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This Manual was prepared by Drs Tammy Meyers (paediatrician Wits Paediatric HIV Working Group), Brian Eley

(paediatrician Red Cross Hospital), Prof. Walter Loening of the National Directorate: Child and Youth Health and members of the South African National Paediatric HIV and AIDS Consensus team, at the request of the Chief Directorate: HIV and AIDS, STIs and Tuberculosis.

Copyright 2005 Department of Health Published by Jacana Media Printed by Pinetown Printers ISBN: 1-77009-172-6 This publication is intended to support HIV and AIDS activities and may be copied and distributed as required. Distribution for remuneration is not permitted. Permission from the copyright holder is required for any changes to the format or content of this publication. All rights reserved. 1st edition: 2005

Guidelines for the management of HIV-infected children

National Department of Health South Africa 2005

CONTENTS
Section 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Guiding principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Principles of medical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . The human immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The pathogenesis of HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Effect on the immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Modes of HIV transmission to children . . . . . . . . . . . . . . . . . . . . . . . . Prognostic factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevention of paediatric HIV-infection . . . . . . . . . . . . . . . . . . . . . . . . Prevention of primary infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prevention of unintended pregnancies among HIV-infected women . . . PMTCT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Laboratory tests to establish HIV-infection of the baby . . . . . . . . . . . . 4 4 4 5 6 7 8 9 9 10 10 10 12

Section 2 Clinical features of HIV-infection . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Opportunities for reaching children in need of HIV care and possible ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Clinical staging of HIV-infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Section 3 Caring for HIV-exposed children . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 HIV-exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 What should be done at clinic visits? . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Section 4 Caring for HIV-positive children . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Health care for HIV-positive children . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Section 5 Nutrition support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Infant feeding choices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutrition intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Guidelines for feeding children with symptomatic HIV-infection . . . . Feeding problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Food supplementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 6 HIV and AIDS clinical manifestations and complications . . . . . . . General danger signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Respiratory conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gastro-intestinal conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Candidiasis (thrush) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Skin conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 26 27 28 29 31 32 32 32 47 55 56

Section 7 Other conditions and opportunistic infections . . . . . . . . . . . . . . . . Cryptococcal meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cytomegalovirus (CMV) infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . Disseminated infection with Mycobacterium avium complex (MAC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HIV encephalopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Wasting syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 8 Paediatric palliative care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Painful conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recommendations for pain control in children . . . . . . . . . . . . . . . . . . . The analgesic ladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 9 Caring for the terminal child . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Supportive care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Indications for inpatient management . . . . . . . . . . . . . . . . . . . . . . . . . . Home care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Section 10 Antiretroviral therapy (ART) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Issues related to paediatric ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Principles for ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Continuity of care units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Function of units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Requirements before ART is implemented . . . . . . . . . . . . . . . . . . . . . . Information recording . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Goals of ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Eligibility for ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treatment of mothers/caregivers/other family members . . . . . . . . . . . ARV drug choices for children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Move from first- to second-line therapy . . . . . . . . . . . . . . . . . . . . . . . . Concomitant tuberculosis (TB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dosage of ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Monitoring for efficacy and safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adverse reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

62 62 63 63 64 65 66 67 68 68 68 69 72 74 74 74 75 75 76 76 77 77 78 79 80 80 81 81 82 82 82 84 85 86 86 88 95

Section 11

Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General consideration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adherence assessment and monitoring . . . . . . . . . . . . . . . . . . . . . . . Adherence to ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

96 96 96 97

Section 12

Post-exposure prophylaxis (PEP) . . . . . . . . . . . . . . . . . . . . . . . . . 102 Universal precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 Procedure for sharps injury or other exposure . . . . . . . . . . . . . . . . 103 Timing of prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Post-exposure prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 PEP following alleged penetrative sexual abuse . . . . . . . . . . . . . . . 106 Legal issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 Guidelines on HIV testing and treatment of orphans and vulnerable children . . . . . . . . . . . . . . . . . . . . . . . . 108 General statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 HIV testing of children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 Counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Pre-test counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Post-test counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Disclosure to children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Reasons for disclosing HIV status . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Guidelines for disclosing HIV status . . . . . . . . . . . . . . . . . . . . . . . . 116 What is the right thing to say? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Interim revised WHO clinical staging of HIV/AIDS for infants and children . . . . . . . . . . . . 118 Appendix 2: Paediatric pain scales . . . . . . . . . . . . . . . . . . . . . . . . 120 Appendix 3A: ARV drugs and TMP/SMZ paediatric dosing chart for use in resource-constrained settings . . . . . . . . . . . . . . . . . . 124 Appendix 3B: Paediatric ARV and co-trimoxazole dosing . . . . . . 128 Appendix 4: ARVs for children side effects and adverse events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Appendix 5: Grading of adverse events . . . . . . . . . . . . . . . . . . . . 132 Appendix 6: Guidelines for adverse drug reaction (ADR) reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 Appendix 7: Adverse drug reaction and product quality problem report form . . . . . . . . . . . . . . . . . . . . . . . . 138

Section 13

Section 14

Section 15

Appendices Appendix 1:

Acronyms and abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

RESOURCES AND ACKNOWLEDGEMENTS


Resources AIDS Helpline: Red Ribbon Resource Centre (for free booklets on ART): Department of Health (Cluster: HIV and AIDS, TB and STIs): Department of Social Development (National HIV and AIDS Co-ordinator): Acknowledgements The development of these guidelines required the collaboration of experts and professionals with in-depth experience in a wide range of matters impacting on the management of HIV-infected and HIVexposed children. The Department of Health wishes to acknowledge and thank all the contributors to this joint effort, as well as the Clinical Care Teams of the Cluster: Maternal, Child, Womens Health and Nutrition and Cluster: HIV and AIDS. List of contributors Razia Bobat Mark Cotton Ashraf Coovadia Hoosen Coovadia Mandla Duma Tumi Funani Liesl Gerntholz Ameena Goga Glenda Gray Ashraf Grimwood Greg Hussey Prakash Jeena Stephanie Jones David Kalombo Leon Levin Walter Loening Eloise Malan Michelle Meiring Harry Moultrie Helena Rabie Anne Robertson Nigel Rollins Paul Roux Haroon Saloojee H Simon Schaaf Gayle Sherman Vincent Thion Avye Violari Nomonde Xundu 0800 012 322 (011) 880-0405 (012) 312-0121 (012) 312-7500

INTRODUCTION
These guidelines are intended to assist health care providers in the management of children who are HIV infected and/or affected, as outlined in the Comprehensive Plan for HIV and AIDS Care, Management and Treatment. In line with the Strategic Plan for HIV and AIDS 20002005, prevention of HIV infection and its early identification are dealt with in detail as they are issues of fundamental importance for everyone dealing with children. The approach adopted is that of the continuum of care, with a holistic patient focus in an integrated health system. The focus is at the primary level within the context of the District Health System being implemented throughout the country. The dynamic nature of the HIV and AIDS field will necessitate that these guidelines be regularly reviewed and updated in order to keep the health care providers informed of advances that impact on the management of the child. This will ensure that the highest possible quality of care is provided. It must be stressed that these guidelines should not be used to exclude any child from receiving treatment when needed.

FIGURES AND TABLES


Figure 1 Figure 2 Figure 3 HIV testing guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical signs of HIV-infection . . . . . . . . . . . . . . . . . . . . . Clinical signs or conditions that may suggest HIV-infection in children . . . . . . . . . . . . . . . . . . . Routine oral Vitamin A supplementation . . . . . . . . . . . . . . Treatment for worms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Amoxycillin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Co-trimoxazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ceftriaxone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Co-trimoxazole prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . Anti-tuberculosis drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . Paracetamol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Paracetamol and codeine phosphate . . . . . . . . . . . . . . . . . . Drug choices for children . . . . . . . . . . . . . . . . . . . . . . . . . . Reasons to move to second-line ART in children . . . . . . . Paediatric ARV regimens and routine monitoring during treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Grading the severity of paediatric adverse reactions (PACTG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Correlation between adherence and virological response to HAART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Assessment of exposure risk, HIV status of source and recommendations for post-exposure prophylaxis (PEP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recommended PEP drug regimen for adults . . . . . . . . . . . 14 17 18 21 22 35 35 36 41 43 70 71 82 84 87 89 99

Table 1 Table 2 Table 3 Table 4 Table 5 Table 6 Table 7 Table 8 Table 9 Table 10 Table 11 Table 12 Table 13 Table 14 Table 15

104 105

Table 16

SECTION 1: INTRODUCTION
Guiding principles
As signatories of the UN Convention of the Rights of the Child, health-care providers in South Africa must comply with the following four principles: I Right to life, survival and development. I Right to equitable treatment and care. I Right to participate in activities and decisions that affect them. I All actions should be based on the best interests of the child. In managing HIV-positive children and their caregivers, apply the following principles, which are consistent with the practice of palliative care medicine: I Do not discriminate. I Be compassionate and show empathy. I Maintain confidentiality at all times. I Establish and maintain clear two-way communication between all levels of the health-care system (clinics and hospitals) regarding management of the child. I Involve all health-care personnel and parents/caregivers in important patient care decisions. I Pay attention to pain and suffering, and preserve quality of life for as long as possible, particularly in the later stages of the illness.

Principles of medical management


While HIV-infection is still not curable at present, it can now be managed as a chronic disease. There are interventions that can significantly improve the childs quality of life and survival time. I Most care and support can be provided at a primary-care level. Where referral is indicated, provide the childs caregiver with a clear explanation of the illness, a referral letter and a follow-up plan.

I I

Caregivers of all children on outpatient care must know the clinical features (danger signs) requiring urgent attention by a health-care provider. As the common childhood infections are also the most frequent cause of illness in HIV-infected children, management is according to well-established Integrated Management of Childhood Illness (IMCI) protocols. However, particular attention needs to be given to the management when the illness becomes persistent or very severe. Prevention of these illnesses is of great importance as they may adversely affect the prognosis. Indiscriminate use of antibiotics should be strongly discouraged to avoid the development of drug-resistant organisms. Limit antibiotic usage to conditions where a bacterial cause is very likely. At all times, consider the possibility of pain and suffering and make every effort to keep the child as comfortable and pain-free as possible. Antiretroviral therapy (ART) suppresses HIV activity and should be given to children who meet certain criteria. Consider terminal care for children with AIDS-defining illnesses.

The human immune system


As HIV and AIDS affect the immune system all health-care providers need to be familiar with some basic facts about the immune system. The system consists of several parts such as: I Polymorphs these are white blood cells with several functions. One of the most important is to attack invading organisms, particularly bacteria. I Lymphocytes these are also white blood cells with different functions to polymorphs. They are programmed to attack other organisms, such as viruses, tuberculosis and fungi. There are sub-groups, such as the CD4 lymphocytes. I Monocytes these are similar to lymphocytes with slightly different functions to lymphocytes.

INTRODUCTION
I

Antibodies these are complex chemical substances that can be found in the serum. They are largely produced by white blood cells as a result of a stimulus, such as an illness or vaccination. Lymphoid tissue is a large number of lymphocytes, which form a structure, such as the regional lymph nodes or glands.

The pathogenesis of HIV


The Human Immunodeficiency Virus (HIV) has certain unusual characteristics. These are responsible for the clinical and laboratory manifestations. HIV carries all its genetic material in two single strands of ribonucleic acid (RNA). It contains no deoxyribonucleic acid (DNA), which is necessary for replication. The virus can survive only in certain human cells, which are then used for replication. Once the HIV has entered the bloodstream it seeks out certain blood and tissue cells. The most important of these are lymphocytes and macrophages, which are types of white blood cells. These cells, in particular CD4 lymphocytes, are targeted by the virus. They have receptor sites to which the virus can attach itself and penetrate into the lymphocyte. The virus also attaches itself to some monocytes and interferes with their function. This results in organ dysfunction. After entry into the cell, viral RNA is converted to a double strand of viral DNA by the reverse transcriptase enzyme. Viral DNA then enters the nucleus of the cell and is incorporated into the host DNA using the integrase enzyme. During cell activation the viral genetic material is replicated, and protein molecules are made and enter the lymphocyte cytoplasm. These particles are split by the protease enzyme and are then assembled and packaged using the cell membrane to create new viruses. Many millions of viruses can be made in this way daily. Eventually the invaded CD4 lymphocytes are destroyed by this process.

Effect on the immune system


The CD4 lymphocytes play an important role in protecting the body against infection. When a large proportion of these lymphocytes has been destroyed immunodeficiency results, which has given the disease its name. The infected CD4 cells are also unable to perform their normal defensive function. As the CD4 count drops the disease manifestations become more severe. The lymphocyte count in the blood varies considerably with age, and reaches adult levels only at the age of about 5 years. Destruction of the cell is brought about by various mechanisms, such as accumulation of viral DNA material. In adults the absolute CD4 count indicates the degree of immune suppression. In children it is the percentage of CD4 cells that is the best indicator. Thus >25% means that there is no immune suppression; 1524% means moderate suppression and <15% means severe suppression. The CD4 count is a good immunological marker of disease progression. Lymphoid tissue/organs become infected at an early stage of the infection with more RNA viral material in these tissues than in the bloodstream. Initially only isolated nodes are affected, but as the disease progresses others are involved. At a late stage of the disease the lymphoid structure collapses and viral particles escape into the circulation.

INTRODUCTION

Modes of HIV transmission to children


I I I

I I

Mother-to-child transmission (MTCT) accounts for most HIV-infected children. Sexual abuse: particularly in countries with a high level of child abuse, such as South Africa. Transmission by blood transfusion: rare as long as transfused blood is carefully screened. There is a risk where the blood donor was in the window period. Insufficiently sterilised instruments, traditional scarification. Wet-nursing with HIV-contaminated breastmilk.

The risk factors for MTCT


Maternal factors High viral load* Low CD4 count Advanced AIDS Low Vitamin A level** Prolonged rupture of membranes Cracked nipples or other breast condition * HIV re-infection may be one of the factors responsible for high viral load during the perinatal period or subsequently. ** Maternal Vitamin A supplementation does not decrease MTCT and may increase the risk of breastmilk transmission. Infant factors Prematurity Breastfeeding Mouth problems Invasive foetal monitoring during labour

Prognostic factors
Without intervention most of the children that are infected at the time of birth will develop features of the disease by 6 months. The disease progresses with opportunistic infections (OIs) becoming apparent and with a downward course much more rapid than in adults. This rapid progression of the disease is largely determined by the immature immune system. There are additional factors that may contribute to the rapid progression, such as the maternal viral load at birth. Some authorities have divided this progression into three categories: Category 1: Rapid progressors die within the first year. (2530%) Category 2: Features of infection appear early in life and disease progresses more slowly with death occurring within 35 years (5060%) Category 3: Long-term survivors who live beyond 8 years of age (525%) Some of the things affecting the prognosis are: I In-utero infection I Signs of infection before the age of 4 months I Maternal high viral load and low CD4 count at time of delivery I Rapid downhill course of the mother I Maternal death

Prevention of paediatric HIV-infection


Effective methods of prevention of paediatric HIV-infection have been well demonstrated both in resource-rich as well as poor countries.

INTRODUCTION

Prevention of primary infection


I I

I I

Reduce heterosexual transmission, ensuring that men are involved in these interventions to reduce the epidemic. Prevent infection during pregnancy and lactation educate men and women about the increased risk of HIV-infection during pregnancy and lactation. Keep adolescent girls and boys in school with appropriate health/sexuality education. Comprehensive management of sexually transmitted infections (STIs).

Prevention of unintended pregnancies among HIV-infected women


I I

Integration of family planning with the prevention of mother-to-child transmission programme (PMTCT). Counselling regarding the dual risk of unintended pregnancies and STIs and HIV.

PMTCT
I I I I

Optimal antenatal care including good nutrition, iron and multivitamin preparations. Addressing all issues that have an increased risk of premature labour. Infection prevention and management, including STIs, urinary infections, malaria and pneumocystis pneumonia. Counselling and HIV testing: every pregnant woman needs to have the necessary counselling and testing for HIV.

10

I I

All HIV-positive mothers need to have infant feeding counselling during the pregnancy and immediately after birth. Every PMTCT programme needs to include, at a minimum, singledose nevirapine given at the onset of labour and to the neonate as soon as possible after birth. Pregnant women meeting the criteria for initiation of ART should receive triple therapy, where possible. Combination AZT and nevirapine has been demonstrated to be highly effective in PMTCT in non-breastfeeding women.

Safer delivery technique


I I

I I I

Most of the MTCT occurs during labour and delivery. The risk is increased by prolonged rupture of membranes, assisted instrumental delivery, invasive monitoring procedures, episiotomy and prematurity. Restrict suctioning of the baby to the presence of meconium-stained liquor. The neonate should be dried carefully at birth. Elective caesarean section reduces the MTCT risk appreciably, but is not recommended as a routine.

11

INTRODUCTION

Laboratory tests to establish HIV-infection of the baby


Currently available tests
I

I I

HIV antibodies are usually detected using the ELISA technique. The test does not distinguish between maternal and the babys antibodies. In the great majority of babies all the maternal antibodies are cleared by the age of 15 months. Rarely they remain up to 18 months. However, if the test is negative before this time, one can assume that the baby is not HIV-infected, provided he is not breastfed any longer. However, if the test is positive at 18 months, the antibodies are being produced by the HIV-infected baby. HIV DNA PCR (polymerase chain reaction) tests for the presence of intracellular HIV DNA material. It is highly sensitive and specific in children from 6 weeks of age. The gold standard infant diagnostic guidelines recommend that 2 concordant HIV DNA PCRs are done at 6 weeks and 4 months to establish whether the infant is truly infected. However, because the test is so sensitive and specific even from 6 weeks of age, one HIV DNA PCR is sufficient provided that the clinical picture matches the laboratory findings. In some areas this test is routinely offered for all babies of HIV-infected mothers in order to establish the infants HIV status as early as possible. It is anticipated that this test will become available for all infants born to HIV-infected mothers in the future. Other tests are being evaluated and may become available for general use. See Figure 1 on page 14 for the recommended testing process.

12

HIV diagnostic protocol for abandoned infants


6 weeks of age 1. HIV ELISA to assess HIV exposure at birth. (Omit if the HIV ELISA of the mother is confirmed positive.) 2. HIV DNA PCR if HIV ELISA of infant or mother* is positive. 3 months of age Repeat HIV DNA PCR to confirm 6-week result. (Omit if HIV ELISA was negative.) Note: 1. A clinical examination to assess for symptoms and signs of HIV-infection should be performed during all visits, and especially at 6 weeks and 3 months of age. The infant should then be followed up as per recommendations for all children (see above). 2. At 6 weeks of age, blood should be taken for both HIV ELISA and DNA PCR tests and the PCR analysed only if the HIV ELISA test result is positive. 3. Postnatal transmission of HIV-infection is likely to be evident by 6 weeks after termination of breastfeeding*. Nevertheless it is recommended that the final qualitative HIV PCR test on abandoned infants be performed 6 weeks after breastfeeding* has stopped. * In most instances information on the mother and breastfeeding will not be available unless hospital records are accessible.

13

14

INTRODUCTION

Figure 1: HIV testing guidelines

AGE <18 MONTHS

AGE >18 MONTHS

Mothers status unknown, and has features of suspected symptomatic HIV

ELISA Mother HIV Positive Positive Negative

I I I

Start co-trimoxazole prophylaxis if child aged 6 weeks Counsel mother on HIV testing Perform ELISA test on mother (with consent) or Test childs ELISA (with consent) if mother cannot be tested

Start co-trimoxazole prophylaxis Do PCR if >6 weeks

Child infected Start co-trimoxazole if indicated (see Section 6 for cotrimoxazole prophylaxis)

Child uninfected (If child still breastfed, repeat ELISA test 6 weeks after breastfeeding has ceased)

ELISA test negative

ELISA test positive

PCR negative

PCR positive

Repeat PCR if HIV asymptomatic*

Child uninfected I Stop co-trimoxazole prophylaxis I Investigate for other causes for illness

I I

Stop co-trimoxazole prophylaxis if not breastfed for 6 weeks Child uninfected if breastfeeding stopped If child still breastfeeding, repeat PCR 6 weeks after stopping breastfeeding. Or if >18 months ELISA can also be done at least 6 weeks after stopping breastfeeding

HIV symptomatic

PCR still positive

Child HIV-infected Manage as per guidelines

Note: *Contact laboratory if results are discrepant. PCR testing may not be available at all centres immediately. In the absence of PCR, perform HIV ELISA testing at 12 and, if positive, at 18 months. PCR = HIV DNA PCR ELISA = HIV ELISA

15

SECTION 2: CLINICAL FEATURES


Opportunities for reaching children in need of HIV care and possible ART
Constant vigilance for HIV-infection in every child that enters a primary health-care facility or hospital is essential. Pro-active steps to detect these children include: I PMTCT records should identify all HIV-exposed children. I Children with severe pneumonia, severe malnutrition, chronic/persistent diarrhoea and TB must be tested for HIV-infection. I Siblings of children diagnosed as HIV-infected should be tested. I Orphans and vulnerable children (OVC) are at special risk of HIV-infection.
N .B .

Every effort must be made to identify children with possible HIV-infection as part of the routine primary-care activities. It is important to identify children that are HIV-infected at an early stage to ensure that they and their families obtain optimal care. As the disease progresses more rapidly in children than in adults, they might be the first to be identified as such in the family. Early identification makes it possible to: I Develop an action plan for regular follow-up and ART if required. I Commence interventions to prevent common childhood infections. I Access social development grants and other support structures. I Approach the family to establish whether others are HIV-infected and offer clinical and social support. See Figure 2 for clinical signs of HIV-infection. An extensive study was undertaken to identify the child with suspected symptomatic HIV-infection. For purposes of IMCI case management Figure 2 below can be used with confidence to classify the child.

16

OF HIV-INFECTION
Figure 2: Clinical signs of HIV-infection
Ask, look and feel for features of symptomatic HIVinfection: I Pneumonia NOW? I Ear discharge ever? I Low weight for age? I Unsatisfactory weight gain? I Persistent diarrhoea now or in the past 3 months? I Enlarged lymph glands in 2 or more sites? I Oral thrush? I Parotid enlargement? If 3 or more features are present, classify the child as suspected symptomatic HIV

If 2 or less features are present, classify the child as symptomatic HIV unlikely

The above clinical features and classification are strongly indicative of HIV-infection. Confirmation of the diagnosis depends on laboratory investigations discussed above. The child that has clinical features suggestive of HIV-infection should be referred for laboratory investigation. Accurate and comprehensive counselling of the caregiver is essential to obtain informed consent for the test(s). Hepato- and splenomegaly are further common features of HIV-infection. However, adding these to the eight features above does not alter the validity of algorithm. Figure 3 on the following page shows a more extensive list to assist with the diagnosis of HIV-infection.

N .B .

17

CLINICAL FEATURES OF HIV-INFECTION


Figure 3: Clinical signs or conditions that may suggest HIV-infection in children
Signs and conditions common in HIV-infected children but uncommon in uninfected: I Severe bacterial infections, especially if recurrent I Persistent or recurrent oral thrush I Bilateral painless parotid swelling I Generalised lymphadenopathy other than inguinal I Hepatosplenomegaly I Persistent or recurrent fever I Neurologic dysfunction I Herpes zoster single dermatome I Persistent generalised dermatitis not responding to treatment Signs and conditions common in HIV-infected children but also common in ill uninfected I Chronic ear infection I Persistent or recurrent diarrhoea I Severe pneumonia I Tuberculosis I Bronchiectasis I Failure to thrive I Marasmus Signs and conditions very specific to HIV-infection I Pneumocystis jiroveci pneumonia (PCP) I Oesophageal candidiasis I Extrapulmonary cryptococcosis I Invasive salmonella infection I Lymphoid interstitial pneumonitis (LIP) I Herpes zoster affecting several dermatomes I Kaposis sarcoma I Lymphoma (not necessarily) I Rectovaginal or rectovesical fistula

18

Clinical staging of HIV-infection


The WHO is developing a 4-stage system, which has yet to be validated and finalised. Previously WHO had developed a 3-stage system, which had been modified by the SA Working Group to reflect local pathology. A 4-stage system has been developed to be similar to the adult 4-stage classification as well as the paediatric classification of the CDC (see Appendix 1, page 118). Stage I: Asymptomatic Stage II: Mild symptoms Stage III: Moderate severity Stage IV: Severe The clinical staging is important because: I It helps to determine the prognosis. I It strengthens the clinical diagnosis when laboratory testing is unavailable or delayed. I It guides the management and consideration for ART. The above clinical features and classification are strongly indicative of HIV-infection. Confirmation of the diagnosis depends on laboratory investigations discussed above. There are many common associated illnesses. Some of the opportunistic infections and illnesses are seen only in association with HIV-infection. These are referred to as AIDS-defining illnesses. (See Sections 6 and 7.) The severity of HIV and AIDS clinical features has been further categorised into stages, which are listed in Appendix 1. The updated WHO staging system will be circulated as soon as it has been finalised.

19

SECTION 3: CARING FOR HIVHIV-exposure


HIV-exposure occurs during pregnancy and birth as well as during breastfeeding. Without any intervention MTCT occurs in about 30% of infants. Interventions such as those mentioned in previous sections can reduce this considerably, particularly if infant feeding is according to the counselling provided. See Section 5. It is important for all health-care providers to be aware of the fact that the risk of dying even for HIV-uninfected children of mothers who have died of AIDS is increased 34 times. This means that particular vigilance and accurate counselling of caregivers is very important at every visit to the primary health-care centre.

What should be done at clinic visits?


Counselling of the mother
I

Potential common HIV-related features, both in the mother or the infant, need to be brought to the mothers attention. Clinical advice should be sought as soon as possible should these occur. The need for implementation of co-trimoxazole prophylaxis for PCP at the age of 6 weeks must be stressed so that she returns to the clinic. A clear follow-up schedule needs to be negotiated.

Growth monitoring
I

I I

This is of particular importance in these children as failure to gain weight is an important indicator of HIV-infection or failure to respond to ART. Weight should be recorded on the Road-to-Health Chart and the curve interpreted. If there is growth failure, intensify assessment for HIV-related features. Also try to identify a treatable cause, e.g. acute or chronic infections (such as respiratory, gastro-intestinal or urinary tract infections or TB). Introduce food supplementation (see Section 5: Nutrition support) after excluding and treating for any infections.

20

EXPOSED CHILDREN
Dietary advice
See Section 5: Nutrition support.

Immunisation
I I I

HIV-infected and HIV-exposed children should be immunised according to the routine national immunisation schedule. BCG can be given routinely at birth. HIV-positive children should receive all vaccinations, including live vaccines.

Table 1: Routine oral Vitamin A supplementation


Routine oral Vitamin A supplementation Target group Non-breastfed infants 0 to 5 months All infants 6 to 11 months Dosage 50 000 IU Schedule A single dose at the age of 6 weeks A single dose at the age of between 6 and 11 months (preferably at 9 months when child comes for immunisation) A single dose at 12 months and then every 6 months until the age of 5 years

100 000 IU

All children 1 to 5 years

200 000 IU

21

CARE FOR HIV-EXPOSED CHILDREN


Treat for worms routinely Table 2: Treatment for worms
Age 1224 months Weight Albendazole <10 kg Avoid in children <24 months. Give 200 mg if necessary >10 kg 400 mg once Mebendazole 100 mg twice daily for 3 days or 500 mg once 500 mg once

>2460 months >5 years Treatment should be repeated every 6 months

Co-trimoxazole prophylaxis
Co-trimoxazole prophylaxis should be provided to children who require it (see co-trimoxazole prophylaxis on page 41).

Counselling and social support


Health-care personnel should: I Be trained in counselling, which should be available at all clinics. Many non-governmental organisations (NGOs), traditional healers and community-based organisations (CBOs) play an increasingly important role in the care of people living with HIV, including assisting with counselling (see Section 14: Counselling). I Take note of local support organisations and resources and refer patients to these organisations whenever appropriate.

22

23

SECTION 4: CARING FOR HIV-POSITIVE


Health care for HIV-positive children
Health care for HIV-positive children includes the following: I Confirmation of the HIV status even where the IMCI classification is that of Suspected Symptomatic HIV-infection. I Staging of the disease is essential for decisions regarding management (see Appendix 1). I Treatment for all infections and opportunistic infections (OIs) must be provided (see Sections 6 and 7). I Regular monitoring of growth and development. I Nutrition support (see Section 5). I Apart from the above, particular attention has to be paid to micronutrient deficiency such as iron and Vitamin A. I Completion of the immunisation schedule. I Preventing infections such as PCP by providing co-trimoxazole prophylaxis. I Counselling of the mother/caregiver (see Section 14). I Consideration for ART (see Section 10).

The HIV-infected child has additional problems


There are indications that the transfer of normal antibodies from the HIV-infected mother to the child may be impaired. The infant is therefore at greater risk of developing measles at a young age. I HIV-infected children are at greater risk of developing primary TB and frequent Haemophilus influenzae infections. I Depression of neutrophils. This increased risk of infection could be addressed by giving: I Additional immunoglobulins to children who have been exposed to measles. I Varicella immunoglobulin, recommended for children who have been exposed to chickenpox. However, this vaccine only protects for 2 weeks.
I

24

CHILDREN
Counselling
Appropriate counselling is ultimately the responsibility of the attending health-care provider. Even though the counselling task can be delegated to a lay counsellor, the health-care provider must make sure that the essential psychosocial issues have been dealt with appropriately. Exit interviews following lay counselling are essential if one is to depend on the counsellor to convey all the essential information. (See Section 14.)

25

SECTION 5: NUTRITION SUPPORT


HIV disease in children often leads to multiple nutritional deficiencies. Decreased intake, impaired absorption and increased nutrient requirements all contribute to this.

Infant feeding choices


HIV-infected women should be counselled during pregnancy about infant feeding choices. HIV may be transmitted by breastmilk and can give an additional 516% risk of infection after birth, depending on the pattern and duration of breastfeeding. Breastmilk does, however, provide the infant with all the required nutrients as well as helping to protect the infant against common infections. Breastmilk also stabilises the intestinal mucosa. This prevents transmission of HIV to the infant. However, this protection is reduced if any other substance, even water, is fed to the infant during this phase of exclusive breastfeeding. Mixed feeding, i.e. breastmilk and formula feeds, which unfortunately is very common, is the worst infant feeding option. Exclusive replacement feeding (exclusive formula feeding) may be difficult in many places, particularly where water, fuel or cleaning utensils and materials are scarce or where the family expects the mother to breastfeed. Exclusive formula feeding under such circumstances subjects the infant to the risk of developing potentially fatal gastroenteritis and other infections. HIV-positive mothers should be counselled on infant feeding options.
N .B .

HIV-negative women and women of unknown HIV status should not be counselled on infant feeding options. They should be supported to exclusively breastfeed for 6 months and to continue breastfeeding for at least 2 years.

26

Where exclusive replacement feeding is acceptable, feasible, affordable, sustainable and safe (AFASS), avoidance of all breastfeeding is recommended. When all these conditions cannot be met, exclusive breastfeeding for the first few months is recommended. Breastfeeding should stop at 6 months or earlier if these conditions can be met. Exclusive breastfeeding can be very difficult for the mother who does not have the support of her family, particularly where disclosure has not taken place. Stigmatisation of the HIV-infected mother then becomes an important factor requiring multiple interventions. The HIV-positive mother who has chosen not to breastfeed must be able to prepare feeds: what volume and strength of feed to prepare, how often to feed the infant and how to use a cup rather than a bottle. Cup feeding should be promoted as cups are easy to clean. During discussions on exclusive replacement feeding, all health-care personnel should abide by the Code of Marketing of Breastmilk Substitutes. Demonstration of replacement milk preparation should be given only to HIV-positive mothers who, after counselling, have chosen not to breastfeed. It must not be given to mothers in the general clinic population. Regardless of feeding choice, mothers need the support of health-care workers for their choice.

Nutrition intervention
The goals of nutrition intervention
I

Appropriate and ongoing counselling of the caregiver: Caregivers of HIV-infected children should receive appropriate nutritional advice recognising cultural and financial constraints. Provide information on food preparation, hygiene, improving energy and nutrient density of meals and examples of nutritious low-cost foods. (See the Chart Booklet, pages 1819.) The particular susceptibility of HIV-infected infants to gut and other infections must be stressed constantly.

27

NUTRITION SUPPORT
I I I I I

Early implementation Enhance immune function Maintain/improve growth Improve quality of life Provide preventive nutrition counselling: Vitamin A-rich foods include: - fortified maize meal and/or bread - carrots, sweet potato, mangoes and pawpaw - dark-green leafy vegetables e.g. morogo/imifino and spinach - liver, eggs, full-cream milk and small fish Iron-rich foods include: - dark-green leafy vegetables - legumes - germinated foods - meat, kidney, spleen, chicken Good sources of antioxidants include: - Vitamin C berries, oranges, dark-green leafy vegetables - Vitamin E nuts, vegetable oils, rice, bran - Selenium nuts, grains, vegetables

Guidelines for feeding children with symptomatic HIV-infection


General advice
I I

Eat small, regular meals 56 times per day. Make the food look and taste good. Children who are sick have a poor appetite. Provide at least 1 fruit and 1 vegetable (not including potato) every day. If there is space at home, plant a vegetable garden, so that vegetables are always available.

28

I I I I

Home-cooked food is better than pre-cooked food in tins or packets. These are expensive and may not be very healthy. Take-away foods like fried chicken are also expensive and not very healthy. Sweets, chocolates and crisps are allowed but should not be eaten in place of food. If these snacks are eaten too often, the child will have no appetite for nutritious food like enriched pap, cereals, vegetables and meat. Dry beans (sugar beans and brown beans) have a nutritional value similar to meat and should be eaten as often as possible. Try to offer at least one portion per day of one of the following: fish, chicken, meat, dry beans, eggs, peanut butter. Add margarine or fish oil when cooking the food. Bread, pap, samp, rice, mealies or other cereal should be eaten as much as the child wants, provided they are mixed with one of the above and/or sour milk to increase the food value. Children with a poor appetite should be encouraged to drink frequently during the day, for example, sour milk, milk, custard, yoghurt, soup or fruit juice. Milk is an important part of the childs diet. After 6 months, the child can drink boiled fresh milk (cows or goats milk). Children over 1 year of age should drink 23 glasses every day of fresh milk or full-cream powdered milk. To increase the nutritional value of soup, add some of the following: fish, oil, margarine, dry beans, meat or bones, milk or milk powder, vegetables. To increase the nutritional value of porridge add some of the following: eggs, sugar, margarine or oil, peanut butter, sour milk or milk.

Feeding problems
The Chart Booklet, page 20, provides management details for feeding problems with infants and young children.

29

NUTRITION SUPPORT
Nausea and vomiting
I I

For the exclusively breastfed child, continue exclusive breastfeeding. For the older child or the child not exclusively breastfed: - Encourage small, frequent meals. - Give food that the child likes. - Allow fluids between meals and not with meals. - Offer cold foods, e.g. jelly, if preferred to warm cooked foods. - Give extra fluids to replace losses from diarrhoea or vomiting (see below). - The child should eat before taking medication. - Dry toast, rusks and dry crackers may relieve nausea. - Avoid food that is too sweet or fatty. - Avoid gravies if they nauseate the child. - Avoid tea and coffee and very salty and spicy foods.

Diarrhoea
Also see Gastroenteritis on page 47. I Increase the frequency and duration of exclusive breastfeeds, where applicable. Only if there is a definite indication give Sugar Salt Solution (SSS) (1 litre of clean or boiled water + 8 level teaspoons of sugar + 1/2 a level teaspoon of salt) or Oral Rehydration Salts (ORS) (one sachet in 1 litre of clean or boiled water) after every loose stool. I If the child is not exclusively breastfed, give food-based fluids such as soft porridge or amasi and SSS or ORS after every loose stool. I Avoid roughage e.g. skin of fruit and beans and peas. I Avoid left-over, stale, old food. I Give freshly prepared food.

30

Sores in the mouth


I I I I I I I

Treat for oral thrush or herpes simplex. Continue exclusive breastfeeding, where applicable. Continue exclusive cup feeding where applicable. Give paracetamol half an hour before solid feeds. Topical anaesthetics Teejel or Bonjela may be helpful. Avoid: acidic (sour) cold drinks like orange juice and hot curried food or chillies. Give: sour milk and porridge, soft and mashed food, ice cream, ice lollies and ice cubes.

Encephalopathy
I I I I

Monitor childs feeding skills by watching the child eat and noting whether swallowing is adequate. Adjust the consistency of the food to the deteriorating developmental level. Modify eating techniques and utensils. Refer to speech therapist for assistance with feeding.

Food supplementation
As part of the Integrated Nutrition Programme, the Protein Energy Malnutrition Scheme addresses the problem of malnutrition in children. Food supplementation is provided for children whose weight has been monitored on the Road-to-Health Chart and is found to be below the 3rd percentile. The programme is administered at primary health-care establishments. Parents/caregivers must also be informed about IMCI feeding recommendations (see the Chart Booklet, pages 1819) and referred to any community support agencies. An additional food supplement Philani and Philani with Zymune is being distributed to all ART service points. It is specifically for children and adult caregivers who are HIV positive and malnourished or at risk of malnutrition.

31

SECTION 6: HIV AND AIDS CLINICAL


As previously noted, most HIV-related conditions present in a similar way to those related to HIV-uninfected children. Management of these conditions is covered in other guidelines, e.g. IMCI. Health-care providers should have a high index of suspicion for conditions associated with HIV, such as opportunistic infections. The necessary knowledge and skills to manage these conditions is essential.

General danger signs


Every child that is examined needs to be checked for any danger signs: I Convulsions with this illness I Lethargic or unconscious I Vomiting everything I Unable to take any feeds These danger signs are an indication that the child is seriously ill and requires urgent referral after appropriate intervention. Danger signs are frequently associated with other problems such as pneumonia, fever or diarrhoea, which obviously also require urgent management.

Respiratory conditions
Respiratory problems are common and in the HIV-infected child frequently pose a high risk.

Community-acquired acute pneumonia


Assess, classify and treat the child according to the IMCI guidelines and the SA National Essential Drug List (EDL). Severe recurrent bacterial pneumonia suggests moderate to severe immune suppression (WHO Stage IlI).

32

MANIFESTATIONS AND COMPLICATIONS


This algorithm applies to children aged 2 months up to 5 years. Severe pneumonia or very severe disease Any general danger sign OR I Chest indrawing OR I Stridor in calm child
I I I I I I I

Give first dose ceftriaxone IM (p. 12) Give first dose co-trimoxazole (p. 8) Give oxygen (p. 13) If stridor: give nebulised adrenaline (p. 12) Test for low blood sugar, then treat or prevent (p. 13) Keep child warm, and refer URGENTLY

Pneumonia
I

Fast breathing (see p. 34 of these Guidelines)

I I I I I

Give amoxycillin for 5 days (p. 8) Soothe the throat and relieve the cough (p. 11) If coughing for more than 14 days, refer for possible TB or asthma Advise mother when to return immediately (p. 21) Follow up in 2 days

Cough or cold
I

No signs of pneumonia or very severe disease

I I I I

Soothe the throat and relieve cough (p. 11) If coughing for more than 14 days, refer for possible TB or asthma Advise mother when to return immediately (p. 21) Follow up in 5 days if not improving

Page references are for the IMCI Chart Booklet, unless otherwise stated.

33

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Chest indrawing means subcostal or lower chest wall recession. Fast breathing: If the child is: 2 months up to 12 months 12 months up to 5 years Management See the Chart Booklet, page 2. i. The child with Severe Pneumonia or Very Severe Disease requires referral for admission. Pre-referral treatment includes: ceftriaxone IM, oxygen, check for hypoglycaemia. Co-trimoxazole in therapeutic doses (Table 4 on the following page) must be given in addition to the above to all children with suspected symptomatic HIV-infection and those who are HIV-infected, confirmed on serology. Many of these patients will have Pneumocystis jiroveci pneumonia (PCP), which causes severe distress and requires immediate and correct management (see below). ii. The children with pneumonia are given amoxycillin according to the schedule on the following page (Table 3). They also require co-trimoxazole in therapeutic doses for 5 days. Here it is important that the child is seen again after 2 days. The mother must be warned that the condition may change suddenly. In that case she must return immediately. Fast breathing is: 50 or more breaths per minute minute 40 or more breaths per minute

34

COMPLICATIONS
Table 3: Amoxycillin
Amoxycillin Given 3 times a day Dose Syrup Syrup mg 125 mg/5 ml 250 mg/5 ml 125 5 ml 187.5 312 500 7.5 ml 12.5 ml 20 ml 10 ml

Weight kg 36 kg 610 kg 1018 kg 1825 kg

Approx. age 0 to 3 months 3 to 12 months 1 to 5 years 5 to 8 years

Caps 250 mg 2 caps

Table 4: Co-trimoxazole
Co-trimoxazole treatment for PCP Given 6-hourly Weight Approx. age Co-trimoxazole dose 6-hourly Less than 5 kg 6 weeks to 2 months 2.5 ml 59.9 kg 2 up to 12 months 5 ml 1014.9 kg 12 up to 24 months 7.5 ml 1521.9 kg 24 up to 60 months 10 ml or 1 tablet >22 kg >60 months 15 ml or 1 1/2 tablets See page 41 for co-trimoxazole prophylaxis.

35

HIV AND AIDS CLINICAL MANIFESTATIONS AND


iii. Infants aged less than 2 months (see the Chart Booklet, page 28): Fast breathing (60 or more breaths per minute) I Severe chest indrawing I Apnoea I Convulsions I Nasal flaring or grunting I Lethargic or unconscious I Movement less than normal I Bulging fontanelle Any of these signs suggest severe bacterial infection and require urgent referral.
I

Table 5: Ceftriaxone
Ceftriaxone given once daily Approx. age Ceftriaxone dose in mg 0 up to 3 months 250 mg 3 up to 12 500 mg months 1 up to 24 750 mg months yrs 24 up to 60 1g months

Weight 3 <6 kg 6 <10 kg 10 <15 kg 1525 kg

Ceftriaxone dose in ml 1.0 ml 2.0 ml 3.0 ml 4.0 (give 2 ml in each thigh)

Hospital management
I I I

Treat according to local hospital guidelines (see following page for suggested management). Apply guiding principles of palliative care. Reassure family.

36

COMPLICATIONS
Investigations Full blood count and differential, blood culture (optimal yield is 30% in bacterial pneumonia), tuberculin skin test (Mantoux), gastric washings/sputum for AFB, chest X-ray. Inpatient treatment I Oxygen I IV fluids I Paracetamol 1015 mg/kg/dose 6 hourly I Ampicillin 100 mg/kg/day IV 6 hourly, changing to amoxycillin as soon as possible I Gentamicin IV <10 years old: 8 mg/kg stat, and then 6 mg/kg daily thereafter >10 years 7 mg/kg stat, then 5 mg/kg daily thereafter I Total duration 710 days, OR I If Staph. aureus infection is suspected: Add cloxacillin 150200 mg/kg/day in 4 doses. Cefuroxime 200 mg/kg/day 8 hourly IV is an alternative ampicillin is then not necessary.
N .B .
I

I I

Have a high index of suspicion for PCP in children under 1 year of age presenting with severe pneumonia. Initiate therapy with co-trimoxazole early as described on page 39, in addition to the management described above. TB can present acutely and should also be considered as part of the differential diagnosis of pneumonia. If there is no improvement within 48 hours of admission, or if the child develops a nosocomial (hospital-acquired) pneumonia, change antibiotics to cover main organisms responsible for nosocomial infection at individual hospital.

37

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Pneumocystis jiroveci (carinii) pneumonia (PCP)
N .B .

PCP is an AIDS-defining disease. PCP occurs most commonly in children under 1 year of age. It is characterised by the following features: I Tachypnoea (fast breathing) I Hypoxaemia (oxygen deprivation characterised by cyanosis) the infant appears to be hungry for air I Sudden onset of fever (not always present) I Absent or low-grade pyrexia Clinical findings on chest auscultation may be negligible and thus not in keeping with the degree of respiratory distress. On chest X-ray one might see a diffuse interstitial infiltrate. Early and appropriate treatment, before the disease has advanced, improves the prognosis significantly. Suspect PCP if the child: I Is less than 12 months old I Has tachypnoea (fast breathing 50 or more breaths/minute in infants 2 to 12 months, 40 or more breaths/minute in children 12 months up to 5 years) I Is dyspnoeic (with severe difficulty in breathing) I Has few crackles relative to the degree of dyspnoea, and decreased breath sound intensity on auscultation I Has cyanosis Begin treating for PCP immediately on suspicion (in addition to usual treatment of pneumonia) (see Tables 4 and 5), even if the HIV status of the child has not been established as yet.

N .B .

All infants and children with suspected PCP should be treated in hospital. It is recommended that the following box be copied, enlarged and pinned up at appropriate places in your establishment.

38

COMPLICATIONS

Inpatient management of suspected PCP


Apply principles of palliative care with emphasis on relieving respiratory distress. Investigations I Check oxygen saturation: - If PCP is present, oxygen saturation is usually less than 90% on pulse oximetry (in room air). I Chest X-ray: - Diffuse bilateral alveolar or interstitial infiltrate (findings can vary). Treatment I Oxygen AND I Co-trimoxazole (20 mg/kg/day of trimethoprim component) 6 hourly IV for 5 days changing to orally for 3 weeks if response adequate AND (Note: this is a higher dose than that used for prophylaxis) I Consider adding clindamycin 3040 mg/kg for severe disease I Prednisone (if PCP confirmed or in presence of hypoxia) 12 mg/kg daily for 2 weeks, AND I Paracetamol 1015 mg/kg 6 hourly for pain or fever >37.5C I Morphine must be given if severe respiratory distress is not responding to other medical management. Morphine oral starting doses (only if ICU is not available): <1 year: 0.20.4 mg 4 hourly 15 years: 0.55 mg 4 hourly 612 years: 57.5 mg 4 hourly (See palliative care.) Remember constipation as side effect of morphine. Co-trimoxazole can cause erythema multiforme/Stevens-Johnson syndrome. If this occurs, stop co-trimoxazole.
N .B .

PCP prophylaxis should continue after discharge as per guidelines (see co-trimoxazole prophylaxis).

39

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Co-trimoxazole prophylaxis for PCP I There is overwhelming evidence that co-trimoxazole prophylaxis prevents PCP. I Co-trimoxazole prophylaxis also protects against invasive bacterial disease. In addition, it protects against other opportunistic infections that include non-typhoid salmonella, toxoplasmosis and Strep. pneumoniae. I It has also been shown to protect against attacks of diarrhoea. Who should receive co-trimoxazole prophylaxis? All HIV-exposed infants from 46 weeks of age. I Any child identified as HIV-infected.
I

How long should co-trimoxazole be given? Co-trimoxazole needs to be given as follows: I HIV-exposed children: until HIV-infection has been ruled out AND the mother is no longer breastfeeding. I HIV-infected children: indefinitely if not on ART. I HIV-infected children on ART: co-trimoxazole can be stopped only when clinical and immunological indicators confirm restoration of the immune system for no less than 6 months. (Also see below.) When can co-trimoxazole prophylaxis be stopped? I Severe adverse drug reaction such as Stevens-Johnson Syndrome, renal or hepatic insufficiency or severe haematological toxicity. I HIV-exposed child: only once HIV-infection has been confidently excluded. I HIV-infected child: do not stop co-trimoxazole if ART is not given. I HIV-infected child on ART: stop co-trimoxazole only when there is evidence of immune reconstitution i.e. in a child 18 months or older with a CD4 count of >15% on 2 occasions no less than 3 months apart. If CD4 count is not available consider stopping cotrimoxazole only after 6 months of good ART adherence with clinical evidence of immune reconstitution. Co-trimoxazole may be of benefit even with clinical improvement.

40

COMPLICATIONS
Drug dosage Co-trimoxazole syrup should be administered once daily, on every day of the week. If syrup is unavailable, crushed tablets may be used. A switch from syrup to tablets can be made to ensure ongoing access to medication. The recommended dose is trimethoprim 68 mg/kg and sulphamethoxazole 20 mg/kg per day. The common preparations of co-trimoxazole have the following formulation: trimethoprim 40 mg and sulphamethoxazole 200 mg per 5 ml. The approximate doses are listed in Table 6.

Table 6: Co-trimoxazole prophylaxis


Co-trimoxazole prophylaxis Weight 6 weeks to 2 months 2 up to 12 months 12 up to 24 months 24 up to 60 months >60 months Approx. age Less than 5 kg 59.9 kg 1014.9 kg 1521.9 kg >22 kg Co-trimoxazole daily dose 2.5 ml 5 ml 7.5 ml 10 ml or 1 tablet 15 ml or 11/2 tablets

If the child is allergic to co-trimoxazole, dapsone is a good alternative (1 mg/kg daily to a maximum of 100 mg).

41

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Tuberculosis (TB)
Diagnosing TB in children can be difficult. It is easy to over-diagnose TB, but it is also easy to miss it. Due to immune deficiency HIV-infected infants and children are particularly susceptible to TB. When to consider TB Suspect TB if the child has: I Contact with an adult who has pulmonary TB. This is often the first indication of childhood TB. I Fever for more than 1 week. I A chronic cough (for more than 3 weeks). I Ongoing weight loss or poor weight gain (crossing percentiles on the Road-to-Health Chart). Investigations Mantoux test: Induration 5 mm represents a positive test. A negative test does not exclude TB. I Gastric washings and/or induced sputum for culture of Mycobacterium tuberculosis (MTB). Also culture other body fluids or tissue obtained by fine needle aspiration. I Radiological: Chest X-ray features are the same in HIV-infected children as in HIV-uninfected children. Interpretation is more difficult in HIV-infected children because of other concurrent lung diseases or other HIV-related conditions presenting in the same way. I Radiological features: alveolar consolidation or hilar lymphadenopathy or cavitation/breakdown, or atelectasis or effusion and/or miliary TB.
I

N .B .

Adequate analgesia should be given to prevent procedural pain e.g. for pleural tap, intercostal drains.

42

COMPLICATIONS
Management, support and prophylaxis Directly observed treatment short course (DOTS) in accordance with Department of Health guidelines for pulmonary or primary TB:

Table 7: Anti-tuberculosis drugs


Pre-treatment body weight 2 months initial 4 months phase treatment continuation phase given 5 times a week treatment given 5 times per week RHZ RH 60, 30, 150 60, 30 1 1 /2 tab /2 tab 1 tab 1 tab 1 1 1 /2 tabs 1 /2 tabs 2 tabs 2 tabs 3 tabs 3 tabs 4 tabs 4 tabs 5 tabs 5 tabs 6 tabs 6 tabs

34 kg 57 kg 89 kg 1014 kg 1519 kg 2024 kg 2529 kg 3035 kg

(RHZ = Rifampicin Isoniazid Pyrazinamide) In those circumstances where children cannot take treatment 5 times a week in the continuation phase and there is guarantee of strict supervision, treatment can be taken 3 times weekly in the continuation phase only. The following table shows the suggested drugs and doses for continuation phase treatment.

43

HIV AND AIDS CLINICAL MANIFESTATIONS AND

Pre-treatment body weight

34 kg 57 kg 89 kg 1014 kg 1519 kg 2024 kg 2529 kg

2 months initial 4 months phase treatment continuation phase treatment given given 5 times a week 5 times per week RHZ RH 60, 30, 150 60, 60 1 1 /2 tab /2 tab 1 tab 1 tab 11/2 tabs 11/2 tabs 2 tabs 2 tabs 3 tabs 3 tabs 4 tabs 4 tabs 5 tabs 5 tabs

(RHZ = Rifampicin Isoniazid Pyrazinamide) Fixed-dose combination tablets available for children RHZ (60, 30, 150 mg), RH (60, 30 mg) and RH (60, 60 mg) only used for the three times weekly regimen. All fixed-dose combination tablets for children are soluble. Recommended dose ranges in mg/kg 3 times a week 5 times a week 812 (10) 46 (5) Isoniazid 812 (10) 812 (10) Rifampicin 3040 (35) 2030 (25) Pyrazinamide 1218 (15) 1218 (15) Streptomycin 2535 (30) 1520 (15) Ethambutol

44

COMPLICATIONS
I

All children with severe forms of TB, such as TB meningitis, miliary TB, or other extra-pulmonary TB should receive in-patient hospital therapy initially and subsequently be considered for referral to TB hospitals for maintenance treatment. These children require at least 9 months of TB treatment. Give paracetamol or tilidine (Valaron) to all children with meningitis for relief of headache (see pain management on pages 6869). As recurrence may occur, all chidren with pulmonary TB should be carefully re-evaluated both clinically and radiologically before discontinuing therapy after 6 months.

Support Caregivers need to receive accurate and detailed information about: I The diagnosis I The need to complete the full course of treatment I The possibility of other family members or close contacts having TB Prophylaxis Routine TB prophylaxis for HIV-infected children is not recommended currently. I Prophylaxis with INH is needed for 6 months if there has been close contact with an adult with pulmonary TB (just as for HIVnegative children) especially if child is less than 5 years of age.
I

N .B .

For more on TB refer to: South African Tuberculosis Control Programme Practical Guidelines 2003.

45

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Lymphoid interstitial pneumonitis (LIP)
Lymphoid interstitial pneumonitis (LIP) is a slowly progressive interstitial lung disease of unknown aetiology. LIP is often asymptomatic, but at times presents with symptoms. It is common and occurs in 40% of HIV-infected children. When to consider LIP HIV-positive child aged more than 1 year with the following: I Recurrent low-grade bacterial infections, chronic lung disease and bronchiectasis I Slowly progressive hypoxia, tachypnoea and exertion fatigue I Clubbing of fingers and/or toes I Enlarged parotid gland I Hepatomegaly Suggestive chest X-ray findings: I Bilateral reticulonodular infiltrates and mediastinal lymphadenopathy Children with LIP often have episodes of intermittent acute pneumonia necessitating antibiotic treatment or admission to hospital. Distinguishing this problem from TB can be difficult. Management I No therapy is required for the asymptomatic child. I Treatment is required for hypoxic children (oxygen saturation consistently <92%) and/or those developing signs of cor pulmonale (right-sided heart failure). I ART is important for the severely affected child. I Prednisone 2 mg/kg daily for 4 weeks for severe cases may also be of help. Thereafter wean to the lowest dose required to maintain oxygen saturation 92%.

46

COMPLICATIONS
I I

I I

I I

Exclude any acute lower respiratory tract infection and pulmonary TB prior to treating children thought to have LIP with steroids. The child will usually be maintained on this lowest dose for life, however, with ART, they may recover and no longer require steroids. All children started on steroids should also be given PCP prophylaxis (see page 40) for as long as they are on steroid therapy. Management of severe or progressive LIP should be carried out in consultation with a specialist HIV clinic, although there is seldom an indication for admission to hospital. Relieve any respiratory distress (see Section 8: Paediatric palliative care). Once treatment has been initiated at the referral level, follow-up and maintenance treatment can be provided at the PHC clinic.

Gastro-intestinal conditions
Acute gastroenteritis
Dehydration is a common cause of mortality and morbidity in children with an acute diarrhoeal episode. It is therefore recommended that the process of assessment and management follows the structure below: Assess dehydration general history and examination consider risk factors consider special types of diarrhoeal illness. Use the IMCI algorithm on the following page and rehydrate immediately where indicated.

47

HIV AND AIDS CLINICAL MANIFESTATIONS AND


IMCI Algorithm 1. Assess hydration. Start by looking to see if enough signs are
present to classify as severe dehydration. If not, try for some dehydration. If still not, then classify no visible dehydration. Signs 2 of the 2 of the following signs following signs Level of Lethargic or Restless and Alert consciousness unconscious irritable Sunken eyes Sunken Sunken Not sunken Ability to Poor or unable Eager, thirstily Normal, not drink thirstily Skin pinch Very slow return Returns slowly Returns (turgor) >2 seconds <2 seconds immediately Hydration Severe Some No visible classification dehydration dehydration dehydration Plan A: Treat for diarrhoea at home Counsel the mother on the 3 rules of home treatment: Give extra fluid, continue feeding and know when to return. a. Give extra fluid (as much as the child will take) I Counsel the mother: - Breastfeed frequently and for longer at each feed. - If the child is exclusively breastfed, provide sugar-salt solution (SSS) in addition to breastmilk. - If the child is not receiving breastmilk or is not exclusively breastfed, give one or more of the following: food-based fluids such as soft porridge, amasi (maas) or SSS or oral rehydration salts (ORS). It is especially important to give ORS at home when: - The child has been treated with Plan B or Plan C during this visit. - The child cannot return to a clinic if the diarrhoea gets worse.
I

Teach the mother how to mix and give SSS or ORS: - To make SSS: 1 litre boiled water + 8 level teaspoons of sugar + 1/2 a level teaspoon of salt. SSS is the solution to be used at home to prevent dehydration. - The contents of the ORS sachet is mixed with clean water and administered to correct dehydration.

48

COMPLICATIONS
I

Show the mother how much fluid to give in addition to the usual fluid intake: - Up to 2 years 50 to 100 ml after each loose stool - 2 years or more 100 to 200 ml after each loose stool Counsel the mother to: - Give frequent small sips from a cup. - If the child vomits, wait 10 minutes. Then continue, but more slowly. - Continue giving extra fluid until the diarrhoea stops. b. Continue feeding c. When to return

Plan B: Treat for some dehydration with ORS Give the clinic-recommended amount of ORS over 4-hour period: Age* Weight Ml for 4 hours Up to 4 months <6 kg 200450 4 months up 12 months to 12 months up to 2 years 6 <10 kg 450800 10 <12 kg 800960 2 years up to 5 years 1219 kg 9601600

*Use the childs age only when you do not know the weight. The amount of ORS needed each hour is about 20 ml for each kg weight. Multiply the childs weight in kg multiply by 20 for each hour. This multiplied by four is the total number of ml over the first four hours. One teacup is approximately 200 ml.
I

Show the mother how to give ORS. - Give frequent small sips from a cup. - If the child vomits, wait 10 minutes. Then continue, but more slowly. - Continue breastfeeding whenever the child wants. - If the child wants more ORS than shown, give more. After 4 hours: - Reassess the child and classify the child for dehydration. - Select the appropriate plan to continue treatment. - Begin feeding the child in clinic.

49

HIV AND AIDS CLINICAL MANIFESTATIONS AND


I

If mother must leave before completing treatment: - Refer if possible. Otherwise: - Show her how to prepare ORS at home. - Show her how much ORS to give to finish the 4-hour treatment at home - Show her how to prepare SSS for use at home. - Explain the 3 rules of home treatment: Give extra fluid, continue feeding and know when to return. Plan C: Treat severe dehydration quickly
Follow the arrows. If answer is YES, read across. If NO, read down.

START HERE
Can you give intravenous (IV) fluid immediately?
YES

Start IV fluid immediately. If the child can drink, give ORS by mouth while the drip is set up. Weigh the child or estimate the weight. Give Ringers Lactate Solution IV (or, if not available, normal saline): Within the first half hour: Rapidly give 20 ml IV for each kilogram weight, before referral (weight x 20 gives ml needed). Repeat this amount up to twice if the radial pulse is weak or not detectable. Plan for the next 5 hours: More slowly give 20ml IV for each kilogram weight, every hour, during referral. Ensure the IV continues running, but does not run too fast.

NO

Is IV treatment available nearby (within 30 min)


NO

YES

REFER URGENTLY to hospital for IV treatment. If the child can drink, provide mother with ORS solution and show her how to give ORS by nasogastric tube. Start rehydration with ORS solution, by tube: give 20 ml per kg each hour for 6 hours (total of 120 ml per kg). REFER URGENTLY for further management. Reassess the child every 12 hours while waiting transfer: - If there is repeated vomiting or abdominal distension, give the fluid more slowly. After 6 hours reassess the child if he is still at the clinic. Classify dehydration. Then choose the appropriate plan of treatment.

Are you trained to use a nasogastic (NG) tube for rehydration?


NO

YES

Can the child drink?


NO

REFER URGENTLY to hospital for IV or NG treatment.

NOTE: If possible, observe the child at least 6 hours after rehydration, to be sure the mother can maintain hydration by giving the child ORS by mouth.

50

COMPLICATIONS
2. Carry out the normal history taking and examination. 3. Look for special risk situations
The following groups of children should be managed in inpatient wards: I infants under 1 month old I malnourished children I children with other danger signs such as: - convulsions with this illness - altered level of consciousness - persistent vomiting - respiratory distress - persistent diarrhoea with dehydration - hypothermia - abdominal distension - dysentery in child <12 months These children should not be managed at primary health-care establishments, but should be referred. Give pre-referral treatment: first dose of antibiotic (IM ceftriaxone) and start rehydration, as required.

4. Look for special types of diarrhoea


Bloody diarrhoea: consider dysentery. Give ciprofloxacin Diarrhoea with high fever/very ill Consider typhoid: refer Persistent diarrhoea (more than 14 days) consider referral (see pages 5254) General management I Continue feeding. I Educate the family on hygiene. I Review in 5 days, but earlier if the child gets sicker. I Advise caregiver when to return immediately, and on home care and prevention of diarrhoea. Fluid management for inpatient care Knowledge about how much fluid is required is essential even when a child is not ill. Maintenance fluids can be given orally or intravenously. Usual fluid requirements for maintenance can be calculated from body weight. Provide 100 ml/kg for the first 10 kg of body weight, 50 ml/kg for the next 10 kg, and 25 ml/kg/day thereafter.

51

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Nutritional management I If breastfed, continue breastfeeding throughout rehydration and maintenance phases of treatment. I If formula fed, restart formula feeds after completion of rehydration (after 4 hours). Drug therapy I Antidiarrhoeal agents are not beneficial and may be harmful. I Diarrhoea episodes do not require antibiotic treatment except in cholera. I Antibiotic treatment may be required in the neonate, in cases of severe malnutrition, severe systemic illness (toxic) or if there is dysentery.

Dysentery
Dysentery presents with blood in the stool with or without mucus. Outpatient management I Refer for inpatient care if: - Child is dehydrated - Child is <12 months - Child unable to tolerate oral medication - No improvement after 2 days of antibiotic - Child is deteriorating I Assess hydration and manage as explained above (acute gastroenteritis). I Continue feeding. I If possible, send stools for microscopy and culture. I Treat with ciprofloxacin as an outpatient - ciprofloxacin dosage: 510 mg/kg/dose 12 hourly for 3 days. I Educate the family on hygiene. I Review after 2 days but earlier if there is deterioration. I Advise caregiver when to return immediately, and on home care and prevention of diarrhoea. Hospital management Ceftriaxone: 2080 mg/kg/day IM daily for 35 days.

52

COMPLICATIONS
Persistent diarrhoea
(>3 liquid stools per day for 14 days or more) This problem is associated with an 11-fold increase in risk of death. Up to 70% of diarrhoeal deaths in HIV-infected children are due to persistent diarrhoea. Outpatient management I Assess and treat for dehydration (see acute gastroenteritis, pages 4752). I Continue feeding: optimal nutritional therapy is a vital component of the management. Nutritional therapy consists of providing easily available, inexpensive and culturally acceptable foods. (See box below.) I Give an additional dose of Vitamin A. (Omit this if the child has had a dose during the previous month.) Feeding recommendations for persistent diarrhoea I If still breastfeeding, give more frequent, longer breastfeeds, day and night. I If taking other milk: - 1st choice is to: replace with fermented milk products, such as amasi (maas) or yoghurt - 2nd choice is to: replace half the milk with nutrient-rich semisolid food (like mashed fruit or vegetables). I For other foods, follow feeding recommendations for the childs age. I Avoid very sweet foods or drink. I Give small, frequent meals at least 6 times a day. I After recovery give one extra meal a day. Follow up in 5 days I Refer for inpatient management if: - Persistent diarrhoea has not improved 5 days after first presentation to health service, despite the child being fed appropriate foods at home. - Child now shows some malnutrition. - Child shows some or severe dehydration.

53

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Hospital treatment for persistent diarrhoea Persistent diarrhoea in HIV-infected children is difficult to manage, particularly if the child is also malnourished. The following management strategies may be attempted: I Correct any dehydration, electrolyte or acid-base abnormalities. I Refer for admission if there is any dehydration. Investigations I Assess for infections elsewhere, e.g. urinary tract infection. I Send a fresh stool for microscopy and culture to the laboratory, to identify atypical or unusual organisms. I Do a lactose test on stools. A simple method of checking stools for reducing substances is to test for the presence of glucose on a urine dipstick of a stool specimen. Feeding If reducing substance is present (>0.5% on Clinitest), try a non-lactose containing feed (e.g. a soya-based formula). I Provide yoghurt (or a similar fermented milk product, e.g. maas) if available. This reduces by one-half the amount of lactose in the child's diet. Give frequent small meals, at least six times a day (see Section 5: Nutrition).
I

Bowel cocktail A bowel cocktail (Bowies regimen) may be tried, although there is inadequate evidence that it is effective: I Cholestyramine 1 g 6 hourly orally for 5 days I Gentamicin 50 mg/kg/day 4 hourly for 3 days given orally Small doses of oral morphine may be useful for intractable diarrhoea (see Section 8: Paediatric palliative care), or Immodium if no cause has been identified.

54

COMPLICATIONS

Candidiasis (thrush)
Oral candidiasis
This is a very common problem in HIV-infected children. If it persists beyond 30 days despite treatment, it is strongly suggestive of HIV-infection. It is at times accompanied by candidial napkin rash. Description This may be confined to the tongue and buccal mucosa and/or extend into the pharynx and/or oesophagus. If it is extensive, it is painful and interferes with eating and swallowing. Outpatient management I Give nystatin (Mycostatin) drops 1 ml 6 hourly 30 mins after feed for 7 days. If the child is breastfed, check for breast thrush and treat the mother accordingly. If the response is poor, add miconazole (Daktarin) oral gel and apply 46 hourly to oral mucosa for 714 days. I Use Gentian Violet, if above medications are unavailable. I Apply medication after meals. I Relieve pain with paracetamol. Topical analgaesia may be of benefit. Use choline salicylate gel (Tegel, Bonjela) or benzymadine mouthwash (Andolex). I Refractory oral candidiasis, or if oesophageal candidiasis is suspected (see page 56): treat with fluconazole 3 mg/kg/day for 21 days. Refer if: I Appropriate medication is unavailable. I The child is unable to feed or is vomiting all feeds.

55

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Oesophageal candidiasis
This is an AIDS-defining illness. Suspect oesophageal candidiasis if a child with oral candidiasis: I Refuses feeds I Has swallowing difficulty I Drools I Has a hoarse voice or stridor Oesophageal candidiasis may occur in the absence of oral candidiasis. I Treat with fluconazole 3 mg/kg/day for 21 days IV changing to oral if tolerating feeds. I Relieve pain.

Skin conditions
Herpes simplex virus
This illness is usually part of an acute primary infection with extensive ulcers in and around the mouth. There may be recurrent infections and at times secondary bacterial infection. Description Painful ulcers 45 mm in diameter can be seen on the tongue, lips and all mucosal surfaces of the mouth. They cause severe pain and interfere with feeding. The child often salivates and drools excessively. Chronic extensive ulcers around mouth and/or nose may also occur. Outpatient management I Oral acyclovir: 2 years and over, give 400 mg 8 hourly for 5 days; under 2 years, give 200 mg 8 hourly for 5 days. I Repeated courses may be required. I If superinfected, give amoxycillin (1025 mg/kg 8 hourly and flucloxacillin 1225 mg/kg per dose 6 hourly max 500 mg per dose) and topical antibiotics may be indicated as well. I Pain relief, as for oral candidiasis.

56

COMPLICATIONS
Refer if: I Appropriate medication is unavailable. I Disseminated infection is suspected (pneumonia, jaundice, abnormal neurological findings). I The child is unable to ingest fluids. I The child is dehydrated. Inpatient management Acyclovir IV 250 mg/m2 8 hourly or 5 mg/kg 8 hourly (cm) x weight (kg) BSA = Height m2
3600

Chickenpox (varicella)
Chickenpox presents with vescicles, which start as papules and eventually become crusted, distributed over face, trunk and limbs. The child with immune suppression may have large and extensive vesicles. Vesicles appear in crops over several days. Mucosal surfaces may also be involved. The child is infectious until all lesions have crusted, therefore they need to be isolated for some weeks. This is particularly important to avoid infecting other HIV-infected children or adults.
N .B .

HIV-infected children, who have been exposed to chickenpox, should be given varicella immunoglobulin. Outpatient treatment I Acyclovir: 80 mg/kg per day orally in 34 divided doses for 714 days. I If secondary bacterial infection develops, add amoxycillin 1025 mg/kg 8 hourly and oral flucloxacillin 1225 mg/kg per dose 6 hourly, with a maximum of 500 mg per dose. I Refer to higher level of care if appropriate medication is not available. I Refer for inpatient management if disseminated infection is suspected (pneumonia, jaundice, abnormal neurological findings), or the child is unable to ingest fluids or the child is dehydrated.

57

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Treatment for disseminated infection Acyclovir IV (500 mg/m2 per dose per day in 3 divided doses for 714 days or 10 mg/kg/dose in 3 divided doses for 714 days). Oral or intravenous antibiotics may be needed if vesicles have secondary bacterial infection.

Herpes zoster
This is a reactivation of varicella. Vesicular lesions usually occur in the region of a dermatome unilaterally and are associated with pain and fever. As zoster is uncommon in children one must suspect HIV-infection.
N .B .

If more than one dermatome is affected, it is an AIDS-defining condition. Outpatient treatment I Acyclovir (80 mg/kg per day orally in 34 divided doses for 710 days) may hasten healing of lesions. I Pain control/relief with paracetamol. I Refer to a higher level of care if appropriate medication is unavailable or disseminated disease is suspected. I Treatment for disseminated infection is as above.

Seborrhoeic dermatitis
This is characterised by eczematous lesions, often with diffuse scaling of scalp (cradlecap), erythema and scaling of the intertrigenous folds and napkin areas. It tends to be severe in HIV-positive children. Secondary bacterial and candidial infection of the rash is common. Outpatient management I Aqueous cream (UEA) as soap. I 1% hydrocortisone cream twice daily to affected areas. I If more severe, try betamethasone valerate 1:10 or 1:4 in UEA and nystatin and terramycin ointment together with steroid cream. I If still unresponsive, add oral antibiotics or prednisone.

58

COMPLICATIONS
Molluscum contagiosum
Papular umbilicated lesions usually occurring around eyes but may be generalised. They may become severe or develop large forms with immunosuppression. Often does not require treatment if mild. Treatment If severe, refer to a specialist centre for: I Liquid nitrogen I Cantharidin paint I Pricking with injection needle I Surgical excision/curettage or electro-surgery with adequate analgesia Extensive lesions respond to nothing except ART. Warts There are widespread common and plane warts. Large genital warts are frequent and extremely refractory to usual modalities of treatment (salicylic paint, cryotherapy, podophyllin, chloroacetic acid). Mild warts may be left alone, refer for management if severe. Treatment Liquid nitrogen is the main therapy I Topical retinoid gels (Adapalene) for extensive flat warts I Application of 50% trichloracetic acid once monthly I Genital warts: 25% podophyllin in Tinct. Benz. Co. applied every two weeks HIV ARV drugs are indicated in severe cases, often resulting in clearing of the warts and decreasing the chance of recurrence.
I

59

HIV AND AIDS CLINICAL MANIFESTATIONS AND


Impetigo
Crusting superficial sores usually occur around mouth or nose. Deeper lesions can be seen on the legs (ecthyma). They are usually caused by Staph. aureus or Strep pyogenes. Lesions can be more severe and recurrent in HIV-positive children. The underlying cause may be insect bites or abrasions that are scratched and become septic. Treatment I Oral erythromycin 10 mg/kg/dose 6 hourly, or cloxacillin 1225 mg/kg/dose 6 hourly orally, or cefalexin 2550 mg/kg/day 8 hourly I Terramycin or Bactroban ointment I Antiseptic soaps are helpful especially for handwashing I Clean, short fingernails I Apply simple antiseptic to abrasions to prevent infection

Tinea (ringworm)
Tinea corporis presents as circular lesions with a raised edge and central clearing on the body. They are itchy at times. Tinea capitis: circular lesions on scalp with alopecia. Extensive infections seen with HIV. Treatment I Whitfields ointment is effective for Tinea corporis I Oral griseofulvin 20 mg/kg/d in two doses for 13 months is indicated for Tinea capitis and severe Tinea corporis I Topical imidazole creams

Dry skin and itching


Aggravated by soaps Treatment I Use UEA or UE (emulsifying ointment) instead of soap I Emulsified bath oils

60

COMPLICATIONS

Drug-related skin reactions


Lesions are very varied ranging from somewhat pigmented patches to extensive shallow ulceration or necrotic skin lesions. The conditions may be severe and life threatening. Types I Maculopapular erythema I Urticaria I Erythema multiforme major (Stevens-Johnson Syndrome [SJS]): target lesions, bullae, skin sloughing, involves mucosal surfaces I Toxic epidermal necrolysis (TEN) (sloughing of epidermis) I Fixed eruption Causative agents I Antibiotics (co-trimoxazole, penicillins, sulphonamides, antiTB drugs) I Phenolphthalene laxatives I NSAIDs I Antiretrovirals I Anticonvulsants Treatment This depends on the severity and the need for the implicated drug. Discontinue suspected drug. Response to stopping drug should be seen within 35 days. Refer for admission I Erythema multiforme I Stevens-Johnson Syndrome I Toxic epidermal necrolysis Outpatient treatment I Topical or oral steroids I Promethazine 0.125 mg/kg 6 hourly orally as needed until the skin rash disappears

61

SECTION 7: OTHER CONDITIONS AND


Cryptococcal meningitis
This presents with signs of meningitis, either acute or with a chronic headache. Often it presents with cranial nerve palsy and usually in older children. It may occur as a result of Immunologic Restitution Inflammatory Syndrome (IRIS). Suspect cryptococcal meningitis when these signs occur in any HIV-infected child.
N .B .

When a lumbar puncture is done the CSF pressure should be measured. Always request laboratories to do India ink stain and cryptococcal antigen on all CSF specimens from HIV-infected children with suspected meningitis.

Other investigations
I I I

Chest X-ray Ophthalmologic assessment Fungal culture of blood and urine

Treatment
All children with suspected cryptococcal meningitis need to be treated initially as inpatients: I Treat with amphotericin B (0.751.0 mg/kg, IV, once daily) for 14 days and/or until there is appropriate clinical improvement. Thereafter change to oral fluconazole (612 mg/kg per day, maximum 400 mg) to complete 810 week course. Acetazolamide and furosemide and serial spinal tap relieve CSF pressure.

Prevention of recurrence
I

After therapy, secondary prophylaxis should be continued indefinitely. Fluconazole (36 mg/kg per day, maximum 200 mg) may be effective. For adolescents receiving ART, maintenance fluconazole may be stopped if immune reconstitution occurs: CD4 count increases to between 100200 cells. There is no evidence available to confirm that stopping maintenance therapy in children is safe.

62

OPPORTUNISTIC INFECTIONS
Cytomegalovirus (CMV) infection
Disseminated disease can present with hepatosplenomegaly, generalised lymphadenopathy, fever and respiratory involvement. Retinitis, CNS manifestations, and infection of the gastrointestinal tract are important additional manifestations. It may also manifest as part of IRIS. Diagnosis can be difficult as presence of antibodies to CMV does not necessarily imply infection. Histological diagnosis is the most helpful.

Treatment
All children with CMV infection need to be treated as inpatients (tertiary):
I

Ganciclovir IV if available (10 mg/kg per day in 2 divided doses over 12 hours for 1421 days, followed by lifelong maintenance therapy with 5 mg/kg per day, IV, 5 days per week). (Specialist team should make the decision whether to treat with ganciclovir.)

Disseminated infection with Mycobacterium avium complex (MAC)


MAC usually presents with disseminated disease in children with HIV-infection. Patients may have pancytopaenia from bone marrow depression and have non-specific signs. Isolated organ disease, especially pulmonary, GIT or skin disease occur less commonly.

Diagnosis
MAC may be isolated from blood (Bactec), bone marrow, lymph node, and other fluids and tissues.

63

OTHER CONDITIONS AND OPPORTUNISTIC INFECTIONS


Treatment
All children need to be referred to a specialist centre for management. Treatment: combination of at least two drugs e.g. clarithromycin + ethambutol or azithromycin + ethambutol (clarithromycin 15 mg/kg/day orally 12 hourly, azithromycin 20 mg/kg/day orally 12 hourly, ethambutol 1520 mg/kg/day orally once a day). Rifabutin (if available) or amikacin may be added. Ciprofloxacin may be of additional benefit. It is advisable to always use 3 or 4 drugs for disseminated disease. Most patients show substantial improvement within first 46 weeks. Therapy should be continued lifelong, irrespective of the extent of improvement. However, if on ART, MAC therapy can be stopped if CD4 percentage has been more than 15% for 6 months and ART has been continued for more than 12 months and the child is asymptomatic.

Toxoplasmosis
Occurs rarely in children. Maternal toxoplasmosis should be sought. Usually presents with encephalitis, with focal neurological abnormalities occurring in association with headache. Outside of the CNS, ocular and pulmonary involvement is the most common.

Diagnosis
Diagnosis may be made on blood and CSF serology. CSF PCR for toxoplasmosis may also be helpful, as is culture of the organism from blood or body fluids. CT scan usually reveals multiple bilateral, focal hypodense ring-enhancing lesions. Placental pathology is helpful if congenital toxoplasmosis is suspected.

Treatment
I

Depends on the extent of CNS involvement and should be individualised. In patients with extensive CNS damage palliative care is recommended. Pyremethamine, sulfadiazine, and leukovorin may be used if available. Management decisions will need to be made by a specialist team. Lifelong treatment is recommended for toxoplasma encephalitis.

64

HIV encephalopathy
HIV-infected monocytes can cross the blood-brain barrier and thus infect the brain. Any part of the nervous system may be affected but in children it is predominantly the brain. It has been estimated that 20% of HIV-infected children may be affected. HIV encephalopathy indicates advanced clinical disease. Diagnosis depends on the presence of at least one of the following findings for at least 2 months: I Failure to attain or regression of developmental milestones or loss of intellectual ability verified by standard developmental scale or neuropsychological tests. I Impaired brain growth, or acquired microcephaly demonstrated by head circumference measurements, or brain atrophy demonstrated by CT scan. I Acquired symmetric motor deficit manifested by two or more of the following: paresis, abnormal reflexes, ataxia or gait disturbances.

Management
This is multidisciplinary and includes the provision of a child dependency grant to support the caregiver. Highly active antiretroviral therapy (HAART) may reverse some of the features of HIV encephalopathy.

Seizures
These may occur in any neurological illness in the HIV-infected child. At times there is no other additional pathology.

Attention deficit disorder and hyperactivity


This is commonly seen and requires specialist attention.

65

OTHER CONDITIONS AND OPPORTUNISTIC INFECTIONS

Wasting syndrome
Wasting syndrome indicates advanced clinical AIDS.

Diagnosis
In the absence of concurrent illness other than HIV-infection or poor access to food that could explain the following features: I persistent weight loss >10% of baseline OR I downward crossing of at least two of the following percentile lines on the weight-for-age chart (e.g. 95th, 75th, 50th, 25th, 5th) in a child 1 year and over OR I <5th percentile on weight-for-height chart on two consecutive measurements, more than 30 days apart PLUS I chronic diarrhoea (i.e. at least two loose stools per day 30 days) OR I documented fever (for 30 days, intermittent or constant)

Comment
Wasting syndrome is a rigorously defined entity. A more practical approach to evaluating the severity of growth and nutritional status is to use the WHO guidelines (Appendix1).

Management
I I

For nutrition advice see Section 5 above. Highly active antiretroviral therapy (HAART) may reverse some of the features of HIV wasting syndrome.

66

Malignancies
Non-Hodgkins lymphomata (NHL) are the most frequent group of malignancies in children with HIV-infection. These include CNS lymphoma and Burkitts lymphoma. Kaposis sarcoma is not uncommon in children with HIV-infection. It has been seen in infants and young children presenting with generalised lymphadenopathy and notably with black/purple lesions on the mucosa of the mouth or on the skin. In some centres it is more common than NHL. Other malignancies include leiomyoma and leiomyosarcoma.

Management
I I I

Refer all children to a specialist centre if malignancy is suspected. Manage the child in association with a paediatric oncologist. Treatment may include HAART and chemotherapy.

67

SECTION 8: PAEDIATRIC
Palliative care is no longer defined as care for those in whom cure is not possible. The expanded definition being promoted in South Africa is: The active, comprehensive care for the physical, emotional and psychosocial needs of the child and the family. It starts when any illness is first diagnosed and continues for the duration of the illness. If and when cure is no longer possible, palliative care will assume the major or total role in the care of the child. Pain and other symptoms are the physical component of palliative care. Pain may be difficult to identify in children. Appendix 2 contains helpful pain scales.

Painful conditions
Conditions that cause pain are frequently found in children with HIV disease. HIV-associated conditions that can cause pain include: I Medical procedures I Severe and/or chronic bacterial, viral, fungal and parasitic infections I Encephalopathy with spasticity I Dental disease I Diffuse lymphadenopathy I Neuropathy I Chronic diarrhoea I Lymphoma

Recommendations for pain control in children


I I I

Establish the cause of the pain. Effectively manage the underlying condition. Developmental appropriate pain scales are available (see Appendix 2). Involve the parent/caregiver when assessing whether pain is present. If in doubt, treat the child and observe the response.

68

PALLIATIVE CARE
I I I

I I I

Pain caused by medical procedures should be anticipated and managed as for HIV-uninfected children. Give medication orally if possible. Give adequate regular analgesic doses, not p.r.n. (as required) doses. Adequate analgesic doses allow children to sleep through the night. Assess pain at regular intervals (24 hourly). Anticipate side effects due to analgesic medication (e.g. constipation) and manage accordingly. Use opioids in doses that effectively control the pain. These doses do not usually result in addiction. When opioids are reduced or stopped, doses should be gradually tapered to prevent severe pain flare-up. Provide palliative care for dying children at home if possible; the local primary health-care service must be able to provide this care or assist NGOs who are providing this care, e.g. in providing essential drug supplies.

The analgesic ladder


Step 1 Mild pain Step 2 Moderate pain Step 3 Severe pain

69

PAEDIATRIC PALLIATIVE CARE


Step 1
I I

Paracetamol, oral, 46 hourly, when required to a maximum of four doses daily Paracetomol syrup 5 ml/8 kg (In between dose for in between weights)

Table 8: Paracetamol
Paracetamol 120 mg/5 ml syrup; 500 mg tablet Weight kg 6 to 10 kg 10 to 18 kg 18 to 25 kg 25 to 50 kg over 50 kg and adult Dose mg 60 120 240 500 1000 Syrup 120 mg/5 ml 2.5 ml 5 ml 10 ml Tab 500 mg 1 2 Approx Age years 3 to 12 months 1 to 5 years 5 to 8 years 8 to 14 years 14 years and older children

Ibuprofen, oral, 46 hourly with food, 410 mg/kg/24 hours. Do not exceed 500 mg per day. Not indicated for children under 5 years.

Step 2
I

Add codeine phosphate syrup to Step 1.

70

Table 9: Paracetamol and codeine phosphate


Weight Age* Chronic pain Paracetamol 46 hrly Chronic severe pain Add codeine phosphate syrup 4 hrly Min Max dose dose 0.2 ml 1.0 ml 0.3 ml 2.0 ml 0.5 ml 3 ml 1.0 ml 5 ml 1.5 ml 6 ml 2 ml 8 ml

2<3 kg 3<6 kg 6<10 kg 10<12 kg 12<16 kg 16<25 kg

03 months 312 months 12 up to 24 years 24 up to 48 years Over 48 months

2 ml 2.5 ml 2.55 ml 57.5 ml 7.510 ml 1012.5 ml

* Use age only if weight not available. Codeine phosphate syrup is given 4 hourly, 0.5 mg/kg (syrup 25 mg/ 5 ml). This can be increased to 12 mg/kg per dose. It is doctor initiated.

Step 3
I I

Paracetamol or ibuprofen can be used with morphine in Step 3. Morphine is doctor initiated.

N .B .

There is no maximum dose for morphine dose is adjusted upward according to the effect on pain. Morphine is given orally 4 hourly according to severity of the pain.
I I

Start with 0.10.3 mg/kg/dose Adjust the dose and frequency according to the effect on pain.

71

PAEDIATRIC PALLIATIVE CARE

Breakthrough pain
Breakthrough pain is pain that occurs before the next regular dose of analgesia. This is due to an inadequate regular dose. I It is recommended that the full dose equivalent to a 4-hourly dose of morphine be administered for breakthrough pain, but it is important that the next dose of morphine be given at the prescribed time, and not be delayed because of the intervening dose. I The dosage should be titrated upward against the effect on pain in the following way: - Add up the amount of breakthrough morphine needed in 24 hours. - Divide this amount by 6 (the number of 4-hourly doses in 24 hours) - The next day increase each dose by that amount. Example: Patient gets 10 mg morphine every four hours. 3 x 10 mg = 30 mg I The patient has 3 episodes of breakthrough pain. 30 mg 6 = 5 mg I The regular 4 hourly dose of 10 mg will be increased by 5 mg. i.e. 10 mg + 5 mg = 15 mg I The increased morphine dose will be 15 mg 4 hourly.
I

72

Referral I Uncontrolled pain I Pain uncontrolled by Step 1 if no doctor available I Severe emotional or other distress which may aggravate the perception of pain Notes regarding morphine use: I Use lower starting doses for younger children (within the age range). I Allow 24 hours before considering a dose increase; increase dose by 3050%. I No maximum dose titrate to analgesic response. I If patient has pain within dosing interval, extra breakthrough doses must be prescribed. I Intravenous morphine should only be used in a hospital or hospice setting. I Opioids have other advantages i.e. they can alleviate intractable diarrhoea and cough.

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SECTION 9: CARING FOR THE


General management
The management of a child who is imminently terminal (death suspected to occur within a few days or weeks) should include: I Relieving distress in the child I Treating easily manageable complications I Limiting hospital admissions I Reducing the duration of hospital stay I Ensuring that parents/caregivers are adequately counselled, and that staff are sympathetic to individual needs The aims are as follows: Maintain good quality of life. I Keep the patient as comfortable as possible. I Provide emotional support to a dying child and the grieving family.
I

Supportive care
The decision to begin supportive (terminal) care is difficult and should be made on a case-by-case basis preferably by a team of professionals with the familys involvement. Once this decision has been made, it should be clearly communicated to other health-care workers involved in the care of the child. This communication can take the form of a letter, which the family may be able to present to other health workers.

74

TERMINAL CHILD
Indications for inpatient management
Hypoxia and respiratory distress IV/nasogastric fluid requirement (beware prolonged use of nasogastric tubes) I Carer(s) unable to cope at home Investigations should be kept to a minimum. They should only be done if it is believed that doing these will shorten the duration of hospital stay or in some way contribute to the childs ultimate comfort. Simple oral antibiotic therapy may be started, where it is thought that a course of antibiotics could shorten the duration of discomfort or hospital stay.
I I

Home care
I I I

I I

Home care of the terminally ill child should be encouraged if the parent(s) or caregiver(s) are able to care for the child at home. There should be no need for intravenous fluids or other intensive treatment. Reassure the parent(s)/caregiver(s) that the child has not been abandoned by the health service, and that they can re-visit the clinic and have the child readmitted to the hospital at any time. Discussions and decisions regarding the institution of home care should be clearly recorded in the childs records. The possibility of chronic/terminal care at a hospice facility should be discussed with parent(s)/caregiver(s) if there are inadequate resources for the care of the child at home.

75

SECTION 10: ANTIRETROVIRAL


Introduction
Every HIV-infected child has the right to comprehensive therapy, which includes ART. It can improve the morbidity and age-related mortality from HIV-infection and in addition improve the quality of life dramatically. Antiretroviral drugs (ARVs) inhibit the process of replication at the level of the enzymes involved. I Nucleoside reverse transcriptase inhibitors (NRTIs) attach to the RNA strand and shorten the transcription of DNA from RNA by the reverse transcriptase enzyme. I Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit the reverse transcriptase enzyme directly. I Protease inhibitors (PI) prevent the new formation of viral particles by inhibiting the protease enzyme. These ARV drugs work best if used in combination of 3, e.g. 2 NRTIs and either an NNRTI or a PI. Highly active ART (HAART) is an ARV combination regimen that can reasonably be expected to reduce the viral load to undetectable levels (i.e. <50 copies/ml) when treating patients with no prior use of ARVs. (Also referred to as ARV-nave.) Absolute eradication of the virus is not achievable as it is also found in lymphoid tissue or the central nervous system, where the ARVs might not reach. If the treatment is stopped or adherence to medication is poor, the virus will replicate to high levels again. Viral genetic material can readily change (mutate) during replication, particularly if the blood level of the ARV is too low to be effective. Consequently there is a strong possibility that the virus then becomes resistant to that drug.

N .B .

It is essential to ensure that adequate levels of the drugs are maintained in the body to prevent the development of resistant strains. It is extremely important that patients are adherent to their medication.

76

THERAPY (ART)
Issues related to paediatric ART
I I I I I I I I I

Children may need special formulation of the drugs, e.g. solutions. Very unpleasant taste can make administration problematic. A caregiver needs to be present constantly to administer the drug. Adherence thus becomes a serious issue. Adjustment of the dosage in relation to the childs growth and organ maturation. ART needs supportive health care, family and community environment. If ART is initiated without such support, it is likely that there will be failure and emergence of resistant viral strains. Guidelines for administering ART to children are different from those of adults. There are relatively few formulations of ARVs available for children.

Principles for ART


I I

I I I I I I I I

Clinical indications may override normal CD4 counts. Do not start too early (for example when the CD4 count is normal and the child is asymptomatic) or too late (when the immune system is irreversibly damaged). Choose drug regimens with proven efficacy. Choose drugs that are unlikely to have serious side effects. The simplest regimens possible should be chosen. Ensure constant availability of ARVs. Ongoing support of the patient and family to maintain adherence. It is important to be vigilant for drug interactions and resistance, which may reduce the potency of ARVs. Patients need to be monitored for adverse reactions. Creative solutions must be found to make sure that vulnerable children, e.g. orphans/children whose parents are ill, get access to ARVs if indicated, e.g. intervention by social worker, peer counsellor or school.

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ANTIRETROVIRAL THERAPY (ART)


I I

For a good response at least 95% of the ARVs need to be taken. (Adherence is the key to successful therapy.) A minority of patients may not respond to ART and continue to deteriorate despite good adherence. (This may occur especially in those who are severely ill before starting ART. Underlying opportunistic infections should be sought.)

Continuity of care units


I I

I I I

In the initial provision of ART, children will be cared for in accredited units. These can be defined as units in primary, secondary or tertiary institutions, where expertise in managing children with ART exists and where ARV stocks are available. Such units will act as resources to train members of staff from other units, so that appropriate care through the health service is provided as quickly as possible. Initially ART delivery will occur at higher levels of health care and will be doctor-initiated as this is where expertise exists currently. As the program expands, provision of this treatment will occur at all levels by doctors and nurses. Stable patients will be referred to those primary care facilities where the necessary expertise, drug stocks and nutritional support are available. Training at all levels of care needs to be implemented immediately so that appropriate referral can occur. Eventually, tertiary care centres will become referral centres for complicated cases and/or ongoing research.

78

Function of units
I I I I I

I I

Staging of children to assess eligibility for ART should occur where the child presents. Possible candidates for ART are then referred to the closest accredited unit. Patients are then re-evaluated for their eligibility for ART. If found not to be eligible, the patient may be referred back to PHC for ongoing management and re-evaluation at regular intervals. At PHC level every effort must be made to maintain the health and nutrition of the child including provision of co-trimoxazole prophylaxis for PCP. As soon as the disease has been found to have progressed, referral for ART must take place immediately. Patients on ART are followed up by the treatment unit for at least 6 months. After this the child may be referred back to the PHC facility for further care. Ongoing care for children on ART includes: - Monitoring treatment adherence - Providing the necessary ARVs on a monthly basis - Referral for laboratory investigations and re-assessment as required - Assessment for drug side effects or other complications - Routine care for immunisation and weight monitoring - Management of intercurrent infections - Provision of co-trimoxazole prophylaxis for PCP - Counselling and support of the parents/caregivers - Arranging for palliative care where appropriate with the support of NGOs The childs home is an important unit that must not be overlooked. Home visits together with a social worker must be encouraged.

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ANTIRETROVIRAL THERAPY (ART)

Requirements before ART is implemented


Within the health-care system
I I I I I I

Supplies of drugs are assured. Staff have the training and skill to manage children on ART. Monitoring mechanisms exist. Supportive processes are in place and active. Effective and informative counselling services are in operation. Management, clinical staff and pharmacists at primary care level and at first referral level must receive adequate and appropriate training.

Within the childs family/environment


I

Parents/caregivers/children understand: - That a responsible individual and a treatment supporter must be identified to administer the drugs every day on a long-term basis - That ART is life-long therapy - The prognosis of the condition - The side effects of the medicines and their mode of action

Information recording
The details of all patients undergoing ART will be captured in a database consistent with the patient information system (PIS) developed by the NDoH. Examples of forms can be obtained.
N .B .

Ensure that data forms are filled in correctly. Accurate information recording is essential for the programme.

80

Goals of ART
The goal of ART for children is to increase survival and decrease HIV-related morbidity and mortality. I The childs CD4 count should rise and remain above the baseline count. I The childs viral load should become undetectable (<400 copies/ml or <25 copies/ml depending on the assay) and remain undetectable on ART.

Eligibility for ART


Patients must satisfy clinical and social criteria before being accepted for treatment.

Clinical criteria
I I I I

Confirmation of diagnosis of HIV-infection. Recurrent (>2 admissions per year) hospitalisations or prolonged hospitalisation (>4 weeks) for HIV-related illness OR The patient satisfies the provisional WHO Stage III/IV disease (see Appendix 1) OR For relatively asymptomatic patients, one can consider CD4 percentage <20% if under 18 months or <15% if over 18 months.

Social criteria
These criteria are extremely important for the success of the programme and need to be adhered to the principle is that adherence to treatment must be at least probable. I At least one identifiable caregiver who is able to supervise the child for administering medication. (All efforts should be made to ensure that the social circumstances of vulnerable children, e.g. orphans, are addressed so that they too can receive treatment.) I Disclosure to another adult living in the same house is encouraged so that there is someone else who can help with the childs ART.

81

ANTIRETROVIRAL THERAPY (ART)

Treatment of mothers/caregivers/other family members


I I I

Always ask about the caregivers health, and the health of other members of the family. Ensure that mothers and other family members access medical care timeously, including ART if needed. Where possible HIV-positive mothers and caregivers requiring medical attention should be attended at the same time as the children to decrease the number of clinic visits, costs and absences from work.

ARV drug choices for children


Table 10: Drug choices for children
Regimen First-line 6 months up to 3 years stavudine (d4T) lamivudine (3TC) Kaletra zidovudine (AZT) didanosine (ddI) nevirapine/efavirenz* Over 3 years and >10 kg stavudine (d4T) lamivudine (3TC) efavirenz (EFV) zidovudine (AZT) didanosine (ddI) Kaletra

Second-line

*Efavirenz if age >3 years, nevirapine if <3 years See Appendix 3 for details.

General comments
I I

All infants under 6 months of age who require ART should be started on treatment under specialist supervision. Stavudine solution requires refrigeration. If no fridge is available, stavudine capsules may be opened and dissolved, and the required amount administered to the child. The rest can be discarded. If the caregiver experiences difficulty with stavudine capsules, zidovudine suspension may be used instead.

82

Switch to tablets or capsules from syrups or solutions as soon as possible. I Children may occasionally need to change a drug from the first-line regimen to one from the second-line regimen, because of intolerance or a serious adverse reaction. Swapping limits the patients second-line treatment options. The decision to swap must be made by a doctor with antiretroviral experience. Swapping of a single drug should only be done if there is full viral suppression, failing which the whole regimen may need to be changed. I If intolerance develops to ritonavir or lopinavir/ritonavir (Kaletra), switch to nelfinavir. I Lopinavir/ritonavir needs to be kept cool (<25C). I Didanosine (ddl) must be taken alone, on an empty stomach, at least an hour before (or 2 hours after) a meal. Tablets should be dissolved in at least 30 ml of water. It is important to use 2 tablets of didanosine to obtain sufficient antacid buffering, e.g. if child needs 100 mg, prescribe 2 x 50 mg tablets. I Abacavir may be used if adverse events occur with other NRTIs. I Drugs not listed in the first- and second-line regimens but mentioned above, e.g. ritonavir, nelfinivir, saquinavir, abacavir, nevirapine, should be available at all tertiary-care centres. I See Table 11 for reasons for moving from first- to second-line ART. For dosage and frequency information on ARVs see Appendix 3.
I

83

ANTIRETROVIRAL THERAPY (ART)

Move from first- to second-line therapy


Consider a move to second-line therapy under the conditions listed in Table 11. For practical purposes, at first and second level it is primarily the clinical features that are of importance.

Table 11: Reasons to move to second-line ART in children


Clinical
I

Immunological
I

Virological
I

Lack of growth or decline of growth in a child showing initial response to treatment despite adequate intake Loss of neurodevelopmental milestones or development of HIV encephalopathy New evidence of Stage III/IV disease (not IRIS: see page 93) Recurrence of prior opportunistic infections e.g. oral candidiasis that is refractory to treatment

No improvement in CD4 value despite therapy (at least 24 weeks) Confirmed return of CD4 percentage (repeated within one month) to baseline or below before starting therapy in the absence of concurrent illness to explain CD4 decline More than 50% decline in CD4 percentage from peak (confirmed within one month) in the absence of concurrent illness to explain CD4 decline

Rebound of viral load to baseline (a detectable viral load may be tolerated in children, providing that growth and elevated CD4 count are sustained)

I I

Short episodes of pneumonia, lower respiratory tract infection and gastroenteritis should not be regarded as clinical failure. Presentation with TB while on first-line therapy is NOT an indication to switch to second-line therapy even though it can present as progression to Stage III/IV disease.

84

Immune reconstitution disease may present as a new Stage III/IV event. However, this will usually be associated with a CD4 count and/or percentage, which have improved over time. This is NOT an indication to switch to second-line therapy. Changing from first- to second-line ART is a decision that is undertaken only after careful consideration. It should not be rushed into before considering possible improvements in managing therapy at home. First check adherence: if it is not possible to improve adherence, attempt directly observed therapy (DOT) with a health-care worker or the trusted other family member or friend identified under social criteria on page 81. Ensure that second-line therapy does not include any drugs used in first-line therapy. It is essential that switching ARV regimens is done in consultation with a paediatrician with ARV experience.

N .B .

I I

Concomitant tuberculosis (TB)


TB occurs commonly with HIV. There are two scenarios to consider:

1. Child presents with TB before starting ART


I

Complete TB therapy if possible before starting ART or delay ART for at least 2 months. (In severe cases it may be necessary to start ART even sooner.) If the child has failed the nevirapine vertical transmission programme or is less than 3 years old or weighs less than 10 kg, use ritonavir as the third drug. If the child was not on the nevirapine vertical transmission programme and is more than 3 years old and weighs more than 10 kg, use efavirenz as the third drug. Monitor ALT monthly if ARV and TB treatment given concurrently.

85

ANTIRETROVIRAL THERAPY (ART)


2. Child develops TB while on ART
I I I I I

If the child is on lopinavir/ritonavir or nelfinavir, then switch to ritonavir. If the child is on nevirapine, and is less than 3 years old or weighs less than 10 kg, switch to ritonavir. If the child is on nevirapine, and is more than 3 years old and weighs more than 10 kg, switch to efavirenz. If the child is unable to tolerate the large number of drugs, ART may have to be interrupted until TB therapy has been completed.* Monitor ALT monthly.

* Discuss all cases with a paediatrician with ARV experience, before interrupting therapy.

Dosage of ART
Provide ARV dosages according to dosing table in Appendix 3. In older children or adolescents ensure that maximum doses for adults are not exceeded.

Monitoring for efficacy and safety


This will have to be carried out at the first referral level, where feasible, in preparation for review of the child at the ARV treatment unit.

86

Table 12: Paediatric ARV regimens and routine monitoring during treatment
Regimen d4T/3TC/lopinavir + ritonavir (Kaletra) Test I CD4 I VL* I Fasting cholesterol I Fasting glucose I Fasting triglycerides** I ALT*** and FBC
I I I

Frequency I Staging, 6-monthly I Baseline, 6-monthly I Baseline, 6-monthly I Baseline, 6-monthly I Baseline, 6-monthly I Baseline, 6-monthly
I I I I I I

d4T/3TC/EFV

CD4 VL ALT and FBC CD4 VL FBC

Staging, 6-monthly Baseline, 6-monthly Baseline, 6-monthly Staging, 6-monthly Baseline, 6-monthly Baseline, then monthly for 3 months, then 6 monthly (with CD4 and viral load) thereafter Baseline, week 2, 4 and 8, thereafter 6 monthly

ddI/AZT/NVP

I I I

ALT

(continues on following page.)

87

ANTIRETROVIRAL THERAPY (ART)


Regimen ddI/AZT/EFV Test I CD4 I FBC Frequency I 6-monthly I Baseline, then monthly for 3 months, then 6 monthly (with CD4 and viral load) thereafter I 6-monthly I 6-monthly I 6-monthly I 6-monthly

ddI/ABC/EFV

I I I

ALT CD4 ALT FBC

Staging = initial testing (screening) for all patients when being referred for antiretroviral therapy. Baseline = testing for ART eligible patients, at initiation of ART. * VL = viral load **For practical purposes it is more convenient to take random samples, and fasting samples if the random sample is abnormal. *** ALT = liver function test It is at the discretion of the initiator of ART to decide whether monitoring for efficacy or toxicity be done outside of the routine schedule.
N .B .

For all regimens a baseline serum lipase will be useful. This may be repeated if there is clinical indication to do so.

Adverse reactions
Also see Appendix 4. ARVs commonly have side effects and occasionally serious adverse events (SAEs) can occur. Side effects are thought to be less common amongst children than amongst adults. Side effects are those reactions to drugs that are known to occur and would be listed in the package insert, e.g. nausea, abdominal pain and vomiting. Life-threatening episodes should be referred to as serious adverse events.

88

Mild side effects include: I Mild nausea, vomiting, diarrhoea I Dizziness (efavirenz) I General malaise I Peripheral neuropathy I Nail discolouration Generally it is recommended that patients continue with the medication if the side effects are mild.

Table 13: Grading the severity of paediatric adverse reactions (PACTG)


Laboratory test abnormalities Item Grade 1 toxicity Grade 2 toxicity 7.08.9 g/dL Grade 3 toxicity <7.0 g/dL Grade 4 toxicity Cardiac failure secondary to anaemia Cardiac failure secondary to anaemia <0.25 x 109/L

Haemoglobin 9.09.9 g/dL 3 months up to 2 yrs Haemoglobin 2 years and over Absolute neutrophil count ALT (SGPT) 1010.9 g/dL

7.09.9 g/dL

<7.0 g/dL

0.751.2 x109/L 1.14.9 x upper normal limit

0.40.749 x 109/L 5.09.9 x upper normal limit 1.548.46 mmol/L 4.4312.92 mmol/L

0.250.399 x 109/L 10.015.0 x upper normal limit 8.4713.55 mmol/L 12.9319.4 mmol/L

>15 x upper normal limit >13.56 mmol//L >19.4 mmol/L

Triglycerides Cholesterol

89

ANTIRETROVIRAL THERAPY (ART)


Clinical adverse events Item Peripheral neuropathy Skin rash/ dermatitis* Grade 1 toxicity Grade 2 toxicity Grade 3 toxicity Grade 4 toxicity

Diagnosis of peripheral neuropathy is difficult in children. Screen motor function against milestones and refer to specialist if peripheral neuropathy is suspected. Exfoliative Vesiculation Diffuse dermatitis OR OR ulcers maculoStevenspapular rash Johnson OR dry syndrome OR desquamation erythema multiforme OR moist desquamation

* See box below for rash due to nevirapine. Adverse reactions will be graded according to the Paediatric AIDS Clinical Trial Group (PACTG) grading.

Action on grading
Also see Appendix 5. I Grades 1 and 2 client remains on therapy. Repeat the test. Reassess clinically within 2 weeks. I Grade 3 test should be repeated within 1 week and if still Grade 3, stop ALL ARV drugs and seek expert medical advice. I Grade 4 Stop all drugs immediately and seek specialist advice. If the patient restarts therapy after the event has resolved, and the same Grade 4 event recurs, appropriate changes or withdrawal of ART may need to be made. A rash in a child on nevirapine with mucosal involvement OR associated with fever/systemic symptoms/derangement in liver functions should be treated as a Grade 4 toxicity. All ARVs should be stopped immediately. Patients at primary care should be referred to a specialist for advice regarding restarting ARVs. The patient should never be rechallenged with nevirapine.

90

Lactic acidosis
All nucleoside analogues have been associated with lactic acidosis. It is a rare but potentially life-threatening metabolic complication of treatment. The pathogenesis is believed to involve drug-induced (NRTI) mitochondrial damage. Initial symptoms are variable; cases have occurred as early as 1 month and as late as 20 months after starting therapy. It is usually associated with combination ddI and d4T.
N .B .

There are no good screening tests to detect lactic acidosis and a high index of clinical suspicion should be maintained. Clinical features: I Generalised fatigue, weakness I Gastro-intestinal symptoms (nausea, vomiting, diarrhoea, abdominal pain, hepatomegaly, anorexia, and/or sudden unexplained weight loss) I Respiratory symptoms (tachypnea and dyspnoea) I Neurologic symptoms (including motor weakness) Laboratory abnormalities: Hyperlactataemia (>2mmol/L) I Increased anion gap [(Na + K) - (Cl + HCO3); normal <15] I Elevated aminotransferases, CPK, LDH, lipase, and amylase I Microvesicular steatosis is seen on histology of the liver
I

N .B .

Discuss management of the patient with a treatment expert. ART should be discontinued in patients with clinical features. Management: Therapy is primarily supportive (fluid, bicarbonate administration and respiratory support). I Administration of riboflavin, thiamine and/or L-carnitine has been reported by some to have benefit in uncontrolled case reports. I Symptoms associated with lactic acidosis may continue or worsen following discontinuation of ART.
I

91

ANTIRETROVIRAL THERAPY (ART)


Hepatotoxicity due to nevirapine
Hepatotoxicity may occur mainly in the first 8 weeks after starting therapy. In the initial phases of therapy ALT should be done frequently (see Table 12). The patient may present with nausea, vomiting, right upper quadrant tenderness and jaundice if severe. Management Grade the level of toxicity as on Table 13. ARVs should be stopped if the toxicity is Grade 3 or 4.
N .B .

Skin rash associated with nevirapine toxicity may occur in association with liver dysfunction. Always check liver function tests if skin rash occurs (see above).

Lipodystrophy syndrome
HIV-associated lypodystrophy includes fat loss and/or fat accumulation in distinct regions of the body: increased fat around abdomen, buffalo hump, breast hypertrophy, and fat loss from limbs, buttocks and face. Other manifestations: insulin resistance, hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia and low HDL levels. These individuals are at risk of type 1 diabetes mellitus and coronary artery disease. Association with ARVs: Usually occurs in patients who have been on long-term therapy. Lipodystrophy is more common in individuals taking stavudine or protease inhibitors. Management There are no established methods for treating lypodystrophy. Encourage exercise to reduce fat accumulation. Some patients improve if switched from a protease inhibitor to an NNRTI. Insulin resistance can be improved with anti-diabetic agents. Lipoatrophy may improve if d4T or AZT is replaced with abacavir. Statins and/or fibrates are effective at lowering cholesterol and triglyceride levels. However drug interactions between statins and ARVs may occur.

92

N .B .

If there is a need to discontinue ART, it is advisable to discontinue all ARVs rather than continuing with one or two agents alone. When a patient discontinues an NNRTIcontaining regime, attempt to continue the NRTI component for 2 days after stopping the NNRTI. (For example, if NNRTI-related hepatotoxicity is suspected.) Adverse events should be recorded and reported regularly to the National HIV and AIDS Cluster. Serious adverse events (SAEs) should be reported within 4872 hours (Grade 4 or death) to the Medicines Control Council. Adverse event forms on yellow paper will be made available at all centres. (Appendix 7) After the patient has recovered from the adverse event it may be possible to recommence therapy with a different regimen. Decision to recommence therapy should be done in consultation with a treatment expert.

Important drug interactions


There are multiple opportunities for serious drug interactions. Therapists are advised to scrutinise package information and seek advice if uncertain.

Immune reconstitution inflammatory syndrome (IRIS)


This is a paradoxical clinical deterioration after starting ART. It is due to the improving immune system interacting with organisms that have colonised the body during the early stages of HIV-infection. Causes A wide range of pathogens may induce IRIS including Mycobacterium tuberculosis (MTB), BCG, Mycobacterium avium complex, Mycobacterium leprae, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus terreus, Candida albicans, Pneumocystis jerovici, CMV, JC virus, human herpes viruses, human papilloma virus and hepatitis B and C viruses (HBV, HCV).

93

ANTIRETROVIRAL THERAPY (ART)


Presentation IRIS usually presents during the first 6 weeks after starting ART. Clinical presentations vary and depend on the causative organism and the organ-system that is colonised. For example IRIS caused by MTB may present with high fever, lymphadenopathy, worsening of the original tuberculous lesion, and/or deteriorating chest X-ray features including the development of a miliary pattern or pleural effusion. Management Includes specific antimicrobial therapy e.g. TB treatment for IRIS caused by MTB. In severe reactions glucocorticosteroids and/or temporary discontinuation of HAART may help.

BCG adverse events


Adverse events related to BCG immunisation have also been reported during immune reconstitution. These include: I Abscess at the site of injection 1015mm I Lymphadenitis (>1.5cm) (lymphadenopathy may also occur at other sites e.g. supraclavicular and cervical) I Suppurative lymphadenopathy in association with BCG injection I Disseminated BCG disease (indicated by failure to thrive, fever, hepatosplenomegaly) I Osteitis I Skin and eye reactions including erythema nodosum, lupus vulgaris and iritis

94

If these reactions are noted, it is important to notify the authorities on a vaccine adverse event form. If an abscess is present, this should be drained to avoid sinus formation. Pus may be sent for TB culture with reference to the fact that a suspected BCG reaction has occurred. In all HIV-infected children with BCG reaction, treatment with INH (20 mg/kg/day), rifampicin and ethionamide (25 mg/kg) should be commenced for a period of 6 months. BCG is PZA resistant, hence the choice of drug regimen. Single anti-TB drugs are usually only available at hospital level, and the patient should be referred appropriately.

Adherence
See Section 11 for details. Adherence greater than 95% will ensure a good virological response and prevent the emergence of viral resistance. Good adherence can be achieved with regular education and support. Adherence may be monitored using diary cards, medication check and other measures. All efforts should be made to encourage this level of adherence.

95

SECTION 11: ADHERENCE


General consideration
Although this section was originally written with adult patients in mind, the difficulties associated with ART for infants and children are highlighted. Adherence to ART is essential to avoid development of drug resistance. It is not possible for health-care providers to reliably predict which caregivers or individuals will be adherent to their treatment plan, as adherence does not correlate with gender, cultural background, socio-economic or education level, or language barriers between provider and patient. It is therefore essential to provide all caregivers with a comprehensive plan to support adherence. Several strategies need to be applied and all members of the health-care team, as well as family and possibly even community-based support groups need to be involved.

Adherence assessment and monitoring


Experience has shown that adherence decreases as time progresses. Monitoring and support of adherence is essential. See the list below for some factors affecting adherence to paediatric ART. A trusting relationship between the patient and caregiver with members of the health-care team is essential. Optimal adherence requires full participation by the health-care team.
N .B .

Every interaction with the patient and caregiver provides an opportunity for reinforcing the absolute need for adherence. Some important factors diminishing adherence in children I Drug side effects and adverse events I Intercurrent illness I Caregiver illness or otherwise occupied I Patient resistance to taking medicines ritonavir alone or in combination with lopinavir has a very bitter taste I Drug stock-outs I Change or absence of patients nurse or doctor I Frequent daily doses e.g. twice or three times per day

96

Supportive and non-judgmental attitudes and behaviours will encourage patient/caregiver honesty about adherence and problems. If adherence problems are noted at a regular follow-up visit, we need to try to contact the family between clinic visits to ensure that there are no problems regarding regular diarising of the treatment. It is also important to remind the caregiver to report any troublesome side effect or illnesses (e.g. investigate new barriers such as transport problems, more frequent visits, get support of family/friends, review counselling). ARV stock-out should never occur; this is an important disincentive for the patient to continue to collect drugs regularly. If the staff member who normally deals with the child is planning a move or vacation, the caregiver needs to be informed of that and reassured that the therapy will continue. Sub-optimal adherence calls for intensified support and further counselling. This is best done by means of a home visit. For all health-care team members, specific training regarding ART and adherence should be offered and updated periodically.

Adherence to ART
Success of ART depends on tablet-taking behaviour. Ideal adherence means a patient must take more than 95% of their doses (i.e. missing less than 3 doses in a month). I If a patient is taking less than 95% of their doses, they are at risk of developing viral resistance and ultimately virological failure. See Table 14 for correlation between adherence and virological response.
I I

N .B .

Patients taking <80% of their doses are unlikely to have any durable virological suppression and should be targeted for adherence improvement urgently. At every follow-up visit this must be reinforced.

97

ADHERENCE
Strategies to promote adherence
I I I I I

I I I I

I I I I I I

Spend time and have multiple encounters to explain goals of therapy and need for life-long adherence. Consider monitoring of medications such as co-trimoxazole or any other drug that is being given prior to ART initiation. Negotiate a treatment plan that the caregiver and patient can understand and to which he/she commits. Encourage disclosure to the child regarding his/her HIV status. Encourage disclosure to family or friends who can support the treatment plan. Adherence is likely to fail if the family is unaware of the problem. Inform caregiver and patient of potential side effects severity, duration and coping mechanisms. Establish readiness to take medications before ART initiation. Provide adherence tools where available: written calendar of medications, pill boxes. Encourage use of alarms, pagers or other available mechanical aids for adherence. Link schedules to daily activities such as mealtimes or tooth brushing. Avoid adverse drug interactions; there must be full disclosure of over-the-counter drugs and traditional medicines. Anticipate, monitor and treat side effects. Include adherence discussions in support groups. Develop links with community-based organisations to support adherence. Encourage links with support groups. Create links with patient advocates.

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Table 14: Correlation between adherence and virological response to HAART


Adherence to HAART* Viral load <400 copies/ml >95% adherence 78% 90% to 95% adherence 45% 80% to 90% adherence 33% 70% to 80% adherence 29% <70% adherence 18% *(number of doses dispensed minus tablets returned) over (number prescribed) e.g. (30-5)/28=25/28=0.9 (90%)

Basic adherence package at initiation


Pre-treatment I Pre-treatment information and education as per visit schedule. I Caregiver and/or patient are introduced to therapeutic counsellor and patient advocate, if available and agreed to or nominated by patient, and home visit is arranged. I Monitoring co-trimoxazole prophylaxis compliance for one month prior to commencing therapy. (This is not to be used to exclude people from ART. It is meant to reinforce daily medication taking behaviour from the outset, and identify potential problems before starting ART). On treatment At each visit: I ART pill or syrup returned needs to be counted or estimated (% doses missed). This is the ideal but this depends on the clinic load and capacity to undertake this intensive activity. Adherence goal is >95% doses taken. Patients with adherence <80% require increased adherence support (see following page). I Tablet/syrup count/estimate may be done before the patient sees the health-care provider, and the count reviewed by the health-care provider during the early/initial visits to evaluate adherence. This does take up time and might not be possible at all sites all the time.

99

ADHERENCE
I I

I I I I

Missed or late clinic visits should trigger concerns about adherence. Routine adherence discussion/education with counsellor is of value. This should be an open-ended discussion, with time for questions and repetition. Feedback from therapeutic counsellors to the rest of team is important to get a better profile of patients and their environment. Encourage caregiver participation in a support group. Continue monthly visit with therapeutic counsellors for first three months and quarterly thereafter. Arrange regular community visits by patient advocates.

Step-up adherence package for people with reduced adherence or virological failure
This applies to all those whose adherence is less than 80% at any visit. (See Table 14.) I The therapeutic counsellor/nurse or doctor needs to re-educate the patient and caregiver (and their buddy) about the importance of adherence. The long-term benefits need to be re-emphasised. I Evaluate the support structures in place. Are they appropriate? How can they be improved? What other options are there? I Consider the use of pillboxes and/or daily dosing diary. I Insist on participation in a support group or link with a patient advocate. I Consider doing a psychological profile. I Check family situation (through social worker and therapeutic counsellor). I Increase home visits by therapeutic counsellors/patient advocates to daily or weekly at a minimum (spot pill counts to be done at home). I Consider directly observed therapy for an agreed period.

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101

SECTION 12: POST-EXPOSURE


Most patient care does not involve any risk of HIV transmission. Each service requires a senior staff member responsible for universal precautions and handling accidental injuries.

Universal precautions
Universal precautions are simple infection control practices used at all times in the care of all patients. The aim is to reduce the risk of transmission of blood-borne infections.

Some preventive measures


Cuts and sores should always be covered. Whenever hands are contaminated with body fluids, they should be washed thoroughly with soap and warm water for at least 10 seconds. I Gloves should be worn to prevent contact with blood or bloodcontaining fluids. I Aprons should be worn in high-exposure areas, e.g. trauma unit, labour ward. I A solution of household chlorine bleach should be used as a disinfectant for surfaces and other inanimate objects. I Spills of body fluids should be cleaned immediately with such disinfectant. I Blood-contaminated material or nappies should be disposed of in a plastic bag with a secure tie. I Children with ongoing bleeding should be separated from the others until such bleeding has stopped. I Human bites and sports injuries carry a very low risk for viral transmission, except if there is mixing of blood from both parties. Precautions need to be taken particularly by all health-care providers to prevent needle-stick injuries.
I I

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PROPHYLAXIS (PEP)
Procedure for sharps injury or other exposure
Each clinic or hospital should ensure that mechanisms to allow the procedure described below are in place before any accident occurs. I Following a sharps injury, immediate first aid should be given, such as flushing the site with running water, hand washing with soap and water, and, where there is bleeding, allowing the site to bleed briefly. I Any exposed mucous membranes should be flushed with large amounts of water. I Antiseptic solutions can have a caustic effect and have not been proven to be effective. However, in the absence of water, antiseptic solutions can be used. I Report injury to supervisor. I Ensure that the Workmans Compensation Act (WCA) form is filled in. I Consult a doctor for assessment of injury and initiation of treatment. I Voluntary confidential counselling should be available immediately, and HIV testing and follow-up counselling made available. I Post-exposure prophylaxis (PEP) with ART can reduce the risk of becoming infected. I Starter-pack kits are available at government hospitals on a 24-hour basis, these include a 2-day course of AZT and lamivudine. The rest of the medication can be received at the hospital dispensary, except for indinavir, which must be obtained by the worker at his/her own expense. The risk of HIV-infection following exposure is outlined in Table 15 on the following page. Many health-care providers find reporting and undergoing voluntary testing and counselling stressful, and some choose to remain silent. This silence is often due to the fear, stigma and discrimination associated with HIV. They will require sensitive support to avoid the very unpleasant consequences.

N .B .

103

POST-EXPOSURE PROPHYLAXIS (PEP)


Table 15: Assessment of exposure risk, HIV status of source and recommendations for post-exposure prophylaxis (PEP)
Percutaneous injury Risk of exposure Recommendation for PEP Consider basic regimen Recommend basic regimen Recommend basic regimen Consider expanded regimen Recommend basic regimen Recommendation for PEP Not recommended Consider basic regimen Recommend basic regimen
(continues on following page.)

Superficial injury, Some risk solid needle Skin puncture, visible High risk blood on needle, hollow needle Needle used in vein or Highest risk artery

Deep intra-muscular injury or injection into body Mucosal and skin contact Unbroken healthy skin Compromised skin, small volume and brief contact Compromised skin, large volume and/or prolonged contact

Highest risk

Risk of exposure Low risk Low risk

Increased risk

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HIV status of source Risk of exposure

Recommendation for PEP Negative Very low Not recommended HIV positive, AIDS or Low for small volumes Consider basic low CD4 and/or high or short duration of regimen viral load skin contact HIV positive, AIDS or High risk for Recommend basic or low CD4 and/or high percutaneous injury expanded regimen viral load depending on the severity of the injury Unknown Consider PEP on a case by case basis

Timing of prophylaxis
I I I

Start as soon as possible, preferably within 12 hours of exposure. The exposure risk should be considered if there is a delay in obtaining prophylaxis. Prophylaxis is of doubtful benefit if started 72 hours after injury.

Post-exposure prophylaxis
Prophylaxis should continue for 28 days. Table 16 outlines the recommended drug regimen.

Table 16: Recommended PEP drug regimen for adults


Drug Zidovudine (AZT) Lamivudine (3TC) Indinavir (IND) in cases of high exposure Dose 300 mg 150 mg 800 mg 8 hourly 28 days Frequency 12 hourly Duration 28 days

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POST-EXPOSURE PROPHYLAXIS (PEP)

PEP following alleged penetrative sexual abuse


Recommended drug regimen I AZT (suspension 10 mg/ml) (see dosing table, Appendix 3) I 3TC (suspension 10 mg/ml) (see dosing table, Appendix 3) I Add Kaletra if significant exposure has occurred For adolescents Tanner stage 34 (Table 10): AZT 300 mg 2 x daily I 3TC 150 mg 2 x daily I Kaletra (optional as above) Duration of prophylaxis is 28 days.
I

Investigations I One must be sensitive about taking blood from a child in a postabuse situation. I Full blood count. I HIV ELISA on both victim and exposure source, where available. I It is useful to know the baseline HIV status; blood for HIV can be taken a few days up to 1 week post-exposure. I Follow up HIV ELISA at 6 weeks, 3 months and 6 months. Victim can be reassured that the likelihood of sero-converting beyond this period is extremely small. Stop prophylaxis if: I Victim is HIV DNA PCR positive (baseline HIV test) I Victim is over 18 months and is HIV ELISA positive I Perpetrator is HIV ELISA negative

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107

SECTION 13: LEGAL ISSUES


Guidelines on HIV testing and treatment of orphans and vulnerable children
Explanatory note: Currently the law does not permit any person other than a parent or legal guardian to consent to HIV testing and medical treatment in the case of a child below the age of 14 years. In the absence of consent from a parent or legal guardian, consent may be obtained from the Minister of Social Development or an application may be made to the High Court. The provisions of the Childrens Bill have widened the scope of who may provide consent by introducing a definition of caregiver and giving this class of persons certain legal rights, which include the right to consent to medical treatment. The Bill also lowers the age of consent to 12 and in cases where a child has sufficient maturity, a child below the age of 12 may also give consent. The Childrens Bill is currently in the process of being passed into law.

General statement
HIV and AIDS presents one of the greatest threats to the wellbeing of children and has a catastrophic effect on the lives of children living in poverty. The loss of many adults to AIDS-related illnesses has meant that children have lost teachers, health-care workers and, most importantly, parents. The lack of an adequate social security net in South Africa means that many children live in informal care settings, without legal guardians to assist them.

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HIV testing of children


HIV testing of any child may only take place if it is in the best interest of the child and if a person legally capable of providing informed consent, provides such consent. The HIV status of an abandoned child needs to be determined as: I Abandoned children have the same rights as other children. I HIV-infection must be excluded as soon as possible to institute appropriate medical management. I Adoptive and foster parents should be aware of the childs health status in order to manage the health needs of the child effectively and to access appropriate support.

Informed consent
Currently, until the Childrens Bill becomes enacted, informed consent to HIV testing and treatment may be provided by the following persons: I The child, if of the age 14 years and of sufficient maturity to understand the benefits, risks, social and other implications of the test I The parent or legal guardian of the child I Managers of childrens homes if the child has been legally placed in the institution

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LEGAL ISSUES
Pre- and post-test counselling
A child must receive age-appropriate pre- and post-test counselling by a trained person, regardless of whether the child is able to provide consent in terms of the Childrens Act. Where the child is not legally able to provide informed consent, the person providing such consent must also receive appropriate pre- and post-test counselling.

Confidentiality
Children above the age of 12 and who are legally able to provide informed consent to an HIV test are entitled to maintain the confidentiality of their HIV status. Consent to disclose the HIV status of such a child must be given by the child. The same principle should apply to children below the age of 12, who are of sufficient maturity to understand the benefits, risks, social and other implications of the test. However, a strict interpretation of the law concludes that the parents and legal guardians of children below the age of 12 may have a legal right to have access to the results of the HIV test. In the case of children below the age of 12 and who cannot consent to HIV testing, consent to disclosure must be given by the persons referred to above.

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111

SECTION 14: COUNSELLING


The following guidelines are provided to assist health workers for counselling of the mother or other caregiver.

Pre-test counselling
I I

I I

I I I I

I I I I

Choose a private area for counselling, where you will not be disturbed or overheard. Assure the client that everything said is confidential. (You could have a poster on your wall making this clear and showing your commitment.) Talk through the reasons for HIV testing of the child and/or the mother. Ask questions in a sensitive way to find out about current and previous risk behaviour. Remember that the client may not know about her/his partners risk behaviour. Find out how much the client already knows and how much he/she wants to know. Offer information about HIV and AIDS. Offer information about the HIV antibody test, including information about the window period of infection. Go through the implications of a positive test result for the client and her/his family, and the emotional responses, e.g. fears, anger, loss, etc. Discuss the clients possible responses to a positive test result. The client can think about who he/she would tell and where to get support. Be aware of what the clients concerns are and let these guide the discussion. For example, if a woman is being counselled and already has children, her major concern may be what will happen to her children if she is HIV positive. Go through the implications of a negative test result. Provide information about how the test is done, how long before the results will be ready, and how the client could obtain the results. Give enough time for the client to consider whether he/she wants to have the test. If the client decides to have the test, obtain consent in writing on the clinic card.

112

Post-test counselling
I I I I I I I

Counselling is essential after the result of the test has become available, irrespective of the result. Always meet with the mother or caregiver as soon as possible. Before speaking to the client familiarise yourself with the facts about the client. Find a private room where you will not be disturbed. Allow the client to express emotion. Allow for silence; time may be needed to absorb bad news. If an HIV ELISA was done in an infant this will reflect the mothers status, but not necessarily that of the infant. In such a case the infants HIV status will be determined by a PCR if <18 months or an ELISA positive result if older (refer to section on infant diagnosis, pages 1415). The parents must therefore be counselled both about their own status and that of their child.

If the result is negative


I I

Deal with the feelings arising from a negative result and explain about the window period. Discuss ways to prevent HIV-infection through safer sex and the importance of remaining negative.

If the result is positive


I I I

I I

Tell the person as clearly and gently as possible. Deal with the immediate feelings. Give the client time to understand and discuss the result. Provide information in a way that the client can understand, provide emotional support and help the person to discuss how he/she will cope. Discuss how the person plans to spend the next few hours and days. Identify what support he/she has.

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COUNSELLING
I

I I I

I I I I I I

Discuss with whom the client wants to share the test result. Find out if the client intends to tell his/her partner. Help the person to decide whether or not to tell him/her immediately and, if appropriate, how to tell him/her. Go through the ways the client can take care of her/his own health and let her/him know about any available treatment. For a pregnant woman, go through the ways she may reduce the risk of MTCT during pregnancy, labour and after the birth. Discuss how she will feed the baby and the importance of exclusive feeding whatever choice she makes. Discussion of co-trimoxazole prophylaxis for the infant and the mother needs to be initiated. Details of this must be discussed at a follow-up session. Identify what difficulties or problems the person foresees and discuss how to deal with them. Encourage the client to ask questions. Where possible and acceptable refer the client to a community organisation for support. Encourage the client to return for a follow-up session when he/she has had time to think about some of the information just provided. If appropriate, some information could be written down as the person is unlikely to be able to remember everything that was said. If the child is HIV-infected, the parent or caregiver must be told what to expect with regard to the health of the child, possible ART and how to care for the child.

114

115

SECTION 15: DISCLOSURE TO


The UN Convention on the Rights of Children (Article 12) states that children have the right to participate in decisions about their own health care. The decision to disclose the HIV status to the child is a difficult one to make.

Reasons for disclosing HIV status


I

I I I

I I I I I

As the age of children living with the disease steadily increases it will result in a population of sexually active young people with HIV-infection. Keeping the secret is a burden. Disclosure should always be in the best interests of the child. This applies to the disclosure itself as well as the manner of disclosure. Benefits of disclosure include recognition of the childs autonomy, increased intimacy with those close to the child, and improved psychological adjustment. The child may need to prepare for tasks ahead (sickness, painful procedures etc.). The child will need to participate in ART adherence. Children often know more than adults think they do. Children not told about their disease often have much more anxiety and distress. Disclosure needs to take place before adolescence.

Guidelines for disclosing HIV status


Many parents/caregivers are afraid to tell their children. They will need encouragement and support to do this. However, it is inadvisable to disclose the status to the child against the wishes of the parent/caregiver. I Where possible get help from trained child counsellors. I Try to balance the needs of the child and the parents. Disclosure is a process, not a once-off event; plan future visits to answer questions and assess how the child is coping with the information. I Assess the childs readiness.

116

CHILDREN
I I

Offer the parents time, support and information. Plan in advance the time, place and people who will be present for the disclosure. However, it is best to avoid a formal, solemn occasion. It may be an advantage to have a written plan of what should be disclosed to the child.

What is the right thing to say?


I I I

I I

I I I I

I I

I I

Find out how much the child knows about the illness and what he/she wants to know. Children need to know that they are loved and will be cared for. Many children believe that sickness is their fault they need reassurance that their illness or their parents illness is not a punishment for a wrongdoing. Children need to learn how HIV is transmitted. The age of the child suggests what can be told to them, e.g. a 5-year-old may not need to hear the word HIV, while an older child can be given more information. Be honest. If you dont know the answer to the childs questions say so and then seek help. Be led by the child in terms of the amount of information he/she requires. Use language appropriate for the childs insight, understanding, education and emotional readiness. Anticipate possible responses by the child and plan for the future; this may include follow-up sessions, counselling and support for the child and parent/family, or education about signs of emotional distress in children. Anticipate the impact of the disclosure on other family members, friends, the school and the community and plan for this. Once the disclosure has happened, monitor the childs behaviour (sleeping, school problems and withdrawal). Changes in behaviour can indicate a need for more support and intervention. Despite the best planning, you cannot be certain how a child will respond. Be respectful of the childs needs, feelings and responses. Stories and books may be useful.

117

APPENDICES
Appendix 1: Interim revised WHO clinical staging of HIV/AIDS for infants and children
(For persons aged under 15 years with confirmed laboratory evidence of HIV infection: HIV antibody if aged 18 months and above; virological or p24 antigen testing if aged under 18 months)

Stage I
I I

Asymptomatic Persistent generalised lymphadenopathy

Stage II
I I I I I I I I I I I I

Hepatosplenomegaly Papular pruritic eruptions Seborrhoeic dermatitis Extensive human papilloma virus infection Extensive molluscum contagiosum Fungal nail infections Recurrent oral ulcerations Lineal gingival erythema (LGE) Angular cheilitis Parotid enlargement Herpes zoster Recurrent or chronic RTIs (otitis media, otorrhoea, sinusitis)

Stage III
I I I I I I I

Moderate unexplained malnutrition not adequately responding to standard therapy Unexplained persistent diarrhoea (14 days or more) Unexplained persistent fever (intermittent or constant, for longer than one month) Oral candidiasis (outside neonatal period) Oral hairy leukoplakia Acute necrotizing ulcerative gingivitis/periodontitis Pulmonary TB

118

I I I I

Severe recurrent presumed bacterial pneumonia Unexplained anaemia (<8g/dl), and or neutropenia (<500/mm3) and or thrombocytopenia (<50 000/mm3) for more than one month Chronic HIV-associated lung disease including bronchiectasis Symptomatic lymphoid interstitial pneumonitis (LIP)

Stage IV
I I I

I I I I I I I I I I I I I I I I I I

Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy Pneumocystis pneumonia Recurrent severe presumed bacterial infections (e.g. empyema, pyomyositis, bone or joint infection, meningitis, but excluding pneumonia) Chronic herpes simplex infection (orolabial or cutaneous of more than one month's duration) Extrapulmonary TB Kaposi's sarcoma Oesophageal candidiasis CNS toxoplasmosis (outside the neonatal period) HIV encephalopathy CMV infection (CMV retinitis or infection of organs other than liver, spleen or lymph nodes; onset at the age one month or more) Extrapulmonary cryptococcosis including meningitis Any disseminated endemic mycosis (e.g. extrapulmonary histoplasmosis, coccidiomycosis, penicilliosis) Cryptosporidiosis Isosporiasis Disseminated non-tuberculous mycobacterial infection Candida of trachea, bronchi or lungs Visceral herpes simplex infection Acquired HIV-associated rectal fistula Cerebral or B cell non-Hodgkins lymphoma Progressive multifocal leukoencephalopathy (PML) HIV-associated cardiomyopathy or HIV-associated nephropathy

119

APPENDICES

Appendix 2: Paediatric pain scales


FLACC scale for determining the intensity of pain of a child who cannot speak (under 3 years or very ill) Score Face 0 No particular expression or smiling 1 Occasional grimace or frown, withdrawn, disinterested Normal position Uneasy, restless, or relaxed tense Lying quietly, Squirming, normal position, shifting back moves easily and forth, tense No crying Moans or (awake or whimpers, asleep) occasional complaint Content, relaxed Reassured by touching, hugging or being talked to, distractible 2 Frequent to constant quivering chin, clenched jaw Kicking or legs drawn up Arched, rigid or jerking Crying steadily, screams or sobs, frequent complaints Difficult to console or comfort

Legs Activity

Cry

Consolability

Each of the categories (F) Face (L) Legs (A) Activity (C) Cry (C) Consolability is scored from 02, which results in a total score between 0 and 10. From The FLACC: A behavioral scale for scoring postoperative pain in young children, by S Merkel and others, 1997, Pediatr Nurse 23 (3), pp. 293-297. Copyright 1997 by Jannetti Co. University of Michigan Medical Center. Reprinted with permission. http://www.childcancerpain.org/content.cfm?content=assess13

120

Faces pain rating scale

0
No pain

1
Hurts a little bit

2
Hurts a little more

3
Hurts even more

4
Hurts a lot

5
Worst pain

Consists of six cartoon faces ranging from a smiling face for no pain to a tearful face for worst pain Recommended age: Children as young as 3 years

Adapted from Nursing Care of Infants and Children, 3rd ed., by LF Whaley and DL Wong, 1987. St Louis: Mosby. Copyright 1987, Mosby. Reprinted with permission. http://www.med.umich.edu/pain/pediatric.htm#ad

Numeric rating scale


Ask the patient to rate their pain intensity on a scale of 0 (no pain) to 10 (the worst pain imaginable). Some patients are unable to do this with only verbal instructions, but may be able to look at a number scale and point to the number that describes the intensity of their pain.

121

APPENDICES
Colour scale
This scale is a coloured stripe in which colour gradually changes from white (no pain) through shades of pink to dark red (worst possible pain). Ask the patient to point to the area on the scale that shows their level of pain. To obtain a number for documentation use the scale parallel to the colour stripe to find the number corresponding to the area where the patient points.

10 9 8 7 6 5 4 3 2 1 0

No pain

122

Word graphic scale


This scale can be used with patients as young as 6 years of age. It uses a line with words to describe pain intensity from no pain to worst possible pain. Show and explain the scale to the patient and then ask him or her to point (or mark) anywhere along the line that shows how much pain they have. To find a number for documentation count the black dots, starting with zero at the far left, to the area where the patient points, up to ten at the far right.

123

APPENDICES

Appendix 3A: ARV drugs and TMP/SMZ paediatric


Weight Abacavir (Ziagen ) Stavudine (Zerit , Lamivudine (Epivir , Zidovudine (Retrovir ,

d4T)
8 mg/kg twice daily 1 mg/kg twice daily

3TC)
4 mg/kg twice daily

ZDV, AZT)
240 mg/m twice daily

Kg

Liquid 20 mg/ml 2 ml 3 ml 4 ml 5 ml 6 ml 7 ml 9 ml 11 ml

Tablet Capsules Liquid 300 mg 15, 20, 30 mg 10 mg/ml 2 ml 15 mg 15 mg or (20 mg) 15 mg or (20 mg) 15 mg or (20 mg)
1

Tablet 150 mg

Liquid 10 mg/ml 7 ml 9 ml 12 ml 14 ml

Capsule 100 mg

56.9 79.9 1011.9 1214.9 1516.9 1719.9 2024.9 25 27.9 25 29.9 28 29.9 3034.9

3 ml 4 ml 5 ml 6 ml 7 ml 9 ml
1

1 cap 1 cap 1 cap 2 caps 2 caps 2 caps

/2 tab /2 tab /2 tab

15 ml 17 ml 20 ml

/2 tab /2 tab /2 tab

20 mg 20 mg

30 mg 12 ml 13 ml 1 tab 1 tab 30 mg

11 ml

1 tab2

24 ml

3 caps or 300 mg tab 3 caps or 300 mg tab 30 ml 300 mg tab

13 ml

1 tab

27 ml

3540

15 ml

1 tab

30 mg

15 ml

1 tab

124

dosing chart for use in resource-constrained settings


Didanosine (Videx , Nevirapine (Viramune , NVP)

DDI)
120 mg/m twice daily Induction dose: 4 mg/kg once daily for first 14 days, then give maintenance dose

Maintenance dose
<8 years 7 mg/kg twice daily 8 years 4 mg/kg twice daily

Chewable tablets Liquid 20, 50, 100 mg 10 mg/ml 2 ml 25 mg + 25 mg 25 mg + 25 mg 50 mg + 25 mg 50 mg + 25 mg 50 mg + 50 mg 50 mg + 50 mg 3 ml 4 ml 5 ml 6 ml 7 ml 9 ml

Tablet 200 mg

Liquid 10 mg/ml 4 ml 6 ml 8 ml 9 ml 10 ml 13 ml

Tablet 200 mg

Liquid 10 mg/ml

Tablet 200 mg

/2 tab /2 tab /2 tab

1 tab am + 1 /2 tab pm 1 tab am + 1 /2 tab pm 9 ml


1

/2 tab

16 ml

/2 tab

100 mg + 25 mg 100 mg + 25 mg 3 caps or 25 mg

11 ml

/2 tab

20 ml

1 tab

11 ml

/2 tab

13 ml

1 tab

13 ml

1 tab am + 1 /2 tab pm 1 tab am + 1 /2 tab pm

100 mg +

15 ml

1 tab

15 ml

(Continued on next page)

125

APPENDICES
Appendix 3A: ARV Drugs & TMP/SMZ paediatric dosing chart for use in resource-constrained settings (Cont.)
Weight Efavirenz (Stocrin , Sustiva , EFV) Lopinavir/ritonavir (Kaletra )

Dose as shown once daily

<15 kg + 12 mg lop/kg 15 kg = 10 mg lop/kg twice daily (lop = lopinavir; r = ritonavir)

Kg

Capsules 50,100, 200 mg

Liquid 80 mg lop/ ml 1.5 ml

Capsule 133.3/ 33.3 mg lop/r

56.9 79.9 1011.9 1214.9 1516.9 1719.9 2024.9 2529.9 200 mg 200 mg 200 mg + 50 mg 200 mg + 50 mg 200 mg + 100 mg 200 mg + 100 mg + 50 mg 3032.9 3034.9 3334.9 3540 200 mg + 200 mg 200 mg + 200 mg 5 ml 3 caps 200 mg + 100 mg + 50 mg 2 ml 2 ml 2.5 ml 2.5 ml 3 ml 3.5 ml 1 cap 2 caps 2 caps 2 caps

4 ml

3 caps

126

Nelfinavir (Viracept )

Trimethoprim/sulfamethoxazole TMP/SMZ (Septrain , Bactrim , various)


4 mg/kg once daily (for prophylaxis against opportunistic illnesses; dose for treatment of bacterial and protozoal infections are higher than listed here)

60 mg/kg twice daily

Tablet 250 mg

Liquid 8 mg/ ml 3 ml 4 ml 5 ml 7 ml 8 ml 9 ml 11 ml 14 ml

Single-strength (SS) tablet 80 mg TMP/ 400 mg SMZ


1

2 tabs 2 tabs 2 tabs 3 tabs 3 tabs 4 tabs 5 tabs 5 tabs

/2 SS tab /2 SS tab

1 SS tab 1 SS tab 1 SS tab 1 SS tab 2 SS tabs

5 tabs

17 ml

2 SS tabs

5 tabs

20 ml

2 SS tabs

127

APPENDICES

Appendix 3B: Paediatric ARV and co-trimoxazole dosing


Paediatric dosing in resource-constrained settings
Developed collaboratively by: 1. Global AIDS Program, Division of HIV/AIDS Prevention National Center for HIV, STD & TB Prevention, Centres for Disease Control and Prevention (CDC), Atlanta, Georgia, USA 2. Home-based AIDS Care Program, Tororo, Uganda Global AIDS Program, CDC Uganda, Entebbe, Uganda 3. Baylor International Pediatric AIDS Initiative Baylor College of Medicine, Houston, Texas, USA 4. The MTCT-Plus Initiative Columbia University Mailman School of Public Health, New York, New York, USA Abacavir Tablets may be swallowed whole, or crushed and dispersed in water or into a small amount of food and immediately ingested. Stavudine Capsules may be opened and dispersed in water or into a small amount of food and immediately ingested. Stavudine capsules are not recommended for use in children <7 kg since dose size from smallest capsule is stable at room temperature for 24 hours or under refrigeration for 30 days. In settings where households do not have access to refrigeration, the oral solution should not be used. In the event that 15 mg capsules are not available, consider giving the 20 mg capsule to children in the 1016.9 kg range. Though these may result in doses higher than the recommended 1 mg/kg dose, higher doses than this have been used in clinical trials and were generally well tolerated. However for children <10 kg a capsule size larger than 15 mg is not advised. Lamivudine Tablets are not scored, but can be divided into two equal halves with a pill splitter in the pharmacy. Tablets may be crushed and dispersed in water or onto a small amount of food and immediately ingested. Oral solution should be used in children <15 kg since accurate dosing with tablets is not practical in smaller children. Oral solution is stable at room temperature. The dose changes from 1/2 to 1 tablet as a child enters this weight range; however, lamivudine has few adverse effects and this dose should be generally well tolerated. Zidovudine Capsules may be opened and dispersed in water or onto a small amount of food and immediately ingested. Tablets may be crushed and dispersed in water or onto a small amount of food and immediately

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ingested. Oral solution should be used in children <7 kg since accurate dosing with capsules is not practical in smaller children. Oral solution is stable at room temperature. Weight-based doses were determined by using body surface area values calculated from typical heights for weight. Didanosine Must use 2 tablets with each dose to provide adequate antacid to buffer stomach acid to allow absorption. The tablets may be dispersed in water before administering. Alternatively, the tablets may be chewed and swallowed. Must be administered on an empty stomach at least 30 minutes before or 2 hours after eating. Oral suspension requires addition of antacid and water and is stable at room temperature for only 24 hours or under refrigeration for 30 days. In settings where households do not have access to refrigeration, the oral suspension should not be used. If taken with indinavir, the drugs must be separated by one hour. Weightbased doses were determined by using body surface area values calculated from typical heights for weight. Nevirapine Tablet is scored and may be divided into equal parts. Tablet may be crushed and dispersed in water or onto a small amount of food and immediately ingested. Oral solution is stable at room temperature. Nevirapine induction dose is 4 mg/kg once daily for 14 days. If no rash develops, it is followed by a maintenance dose of 7 mg/kg twice daily for children <8 years old, or 4 mg/kg twice daily for children >8 years old. Consider using liquid for the induction dose in children in this weight range to give a more precise dose. If using tablets for children in this weight range, this chart suggests 1 tablet in the morning and 1/2 tablet in the afternoon to yield a dose that approximates that of the liquid. The halflife of nevirapine is long enough that the fluctuation in drug levels from this staggered dose is considered clinically acceptable. Efavirenz Capsules may be opened and dispersed in water or onto a small amount of food and immediately ingested. Oral solution is stable at room temperature. Dose for oral solution is greater than that for capsules or tablets. The dose and pharmacokinetics of the oral solution are not as well established as with the capsules and tablet. Thus, although the liquid may be available in some areas, it is advisable to use the capsule or tablet forms when possible. Lopinavir/ritonavir Dose is calculated based on lopinavir component. Capsules may NOT be opened or crushed and must be swallowed whole, but may be used for children who can swallow capsules. Capsules or oral solution should be taken with food. Capsules and oral solution must be refrigerated until dispensed. After removal from refrigeration, capsules and

129

APPENDICES
oral solution are only stable for 60 days at room temperature (up to 25C). Where temperatures are expected to exceed 25C, the feasibility of dispensing smaller amounts and giving more frequent refills should be considered (for example, no more than monthly supplies dispensed at one time). Lopinavir/ritonavir is not recommended for children <6 months old. The amount of solution has been rounded up to the nearest 1 /2 ml from manufacturers recommendation for easier measurement. In the 1719.9 kg range, two capsules twice daily would result in a dose that is 4060% higher than recommended, however, using only one capsule twice daily would result in a dose that is 2030% lower than recommended. Consider liquid for children in this weight range. Nelfinavir Tablets may be crushed and dispersed in water or onto a small amount of food and immediately ingested. Must be taken with food to improve absorption. Oral powder for administration requires complicated administration technique that may not be practical in resource-poor settings. Doses for children <2 years of age are not well established. The dose listed for children <10 kg is within a range of up to 75 mg/kg twice daily. This has been used for small children by some clinicians. Indinavir Capsules may be opened and dispersed in water or onto a small amount of food and immediately ingested. Must be taken on an empty stomach (1 hour before or 2 hours after a meal). Patients must drink lots of water during the day while taking indinavir to prevent development of kidney problems. If taking didanosine, the drugs must be separated by one hour. Weight-based doses were determined by using body surface area values calculated from typical heights for weight. Trimethoprim/sulfamethoxazole Recommendations for prophylaxis against opportunistic infections for HIV-infected children are to give 5 mg/kg twice daily for 3 consecutive days/week. Considering the dosage strength of the TMP/SMZ suspension and in efforts to support medication adherence, dosing children once daily every day of the week may be simpler. The dose of 4 mg/kg is an easy conversion from the childs weight to the mls of suspension because the 8 mg/ml dosage strength of the TMP/SMZ suspension allows the dose to be calculated as 1 /2 ml of suspension per kg. Doses are higher for treatment of bacterial and protozoal infections and other sources should be consulted.

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Appendix 4: ARVs for children side effects and adverse events


Side effects and adverse events of ARVs in children
Class NRTI Drug Zidovidine (Retrovir ) Didanosine ddI (Videx ) Side effects/adverse events Anaemia, granulocytopenia, myopathy, lactic acidosis Common: abdominal pain, nausea and vomiting Uncommon: pancreatitis, peripheral neuropathy, lactic acidosis Stavudine Common: headache, rash, gastrointestinal (Zerit ) Uncommon: pancreatitis and peripheral neuropathy, lactic acidosis Abacavir Hypersensitivity reaction (with or without rash) may be fatal in adults and children (Ziagen ) Lamivudine Common: headache, fatigue and abdominal pain (3TC) Uncommon: pancreatitis and peripheral neuropathy, lactic acidosis Nevirapine Skin rash, sedative effect and diarrhoea (Viramune ) LIVER TOXICITY Efavirenz Skin rash CNS Sleep disturbance, confusion, abnormal (Stocrin ) thinking. Teratogenic in primates Ritonavir Nausea, vomiting, diarrhoea (Norvir ) Hypercholesterolaemia and hypertriglyceridaemia Nelfinavir Diarrhoea (Viracept ) Can exacerbate chronic liver disease Hypercholesterolaemia and hypertriglyceridaemia Nausea, vomiting, diarrhoea Kaletra Hypercholesterolaemia and hypertriglyceridaemia

NNRTI

PI

131

APPENDICES

Appendix 5: Grading of adverse events


Feature Haematology Haemoglobin (g/dL) Age >2 yrs Absolute neutrophil count Platelets (cells/mm) Gastro-intestinal Bilirubin AST ALT GT Pancreatic Amylase Abdominal pain Diarrhoea Grade 1 1010.9 Grade 2 79.9 Grade 3 <7.0 Grade 4 Cardiac failure 2 to anaemia

0.750 1.2

0.4000.749 50 00075 000

0.250.399 25 00049.999

<0.250 <25 000 or bleeding

1.11.9 x N* 1.14.9 x N 1.14.9 x N 1.14.9 x N 1.11.4 x N Mild Soft stools

2.02.9 x N 5.09.9 x N 5.09.9 x N 5.09.9 x N 1.51.9 x N Moderate No Rx needed Liquid stools

3.07.5 x N 10.015.0 x N 10.015.0 x N 10.015.0 x N 2.03.0 x N Moderate Rx needed Liquid stools + mild dehydration, bloody stools Severe Severe, little oral intake >3 episodes/ day or duration >7 days Mild urticaria >40C

>7.5 x N >15.0 x N >15.0 x N >15.0 x N >3.0 x N Hospital and Rx Severe dehydration or hypotensive shock Distention + vomiting Unable to take any food or fluid for >24 hrs Intractable vomiting

Constipation Nausea

Mild Mild

Moderate Moderate

Vomiting

<1 episode/ 13 episodes/ day day or duration >3 days Allergic/dermatalogical Allergy Itch without Itchy rash rash Drug fever 38.540.0C Cutaneous

Diffuse macu- Vesiculation, papular rash dry ulcers desquamation

Severe urticaria Anaphylaxis, angioedema Sustained fever: >40C >5 days Exfoliative dermatitis, StevenJohnson or E. multiforme, moist desquamation

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Feature

Grade 1

Grade 2

Grade 3 Changes not improved with drugs or other therapy: or onset of confusion, memory loss, lethargy, sedation, or somnolence not resolved by rest See below**

Grade 4 Delirium, obtundation, coma or psychosis or Grade 3 toxicity with no response to dose reduction

Nervous system Mental status or Changes with Changes behaviour normal requiring drugs function or other therapy: or mild lethargy, sedation, or somnolence that resolves with rest

Neuropathy/ lower motor neuropathy Other Clinical symptoms not otherwise specified above

None

Mild transient parathesia

See below***

No therapy, monitor condition

May require Requires Requires active medical minimal care or possible intervention, hospitalisation intervention and hospitalisation or hospice care monitoring

* N = normal ** Persistent or progressive parasthesias, burning sensation of feet or mild disethesia, no weakness, mild tendon reflex changes, no sensory loss. *** Onset of significant weakness, decrease or loss of DTR, sensory loss in stocking-glove distribution, multiple cranial nerve involvement; bladder or bowel dysfunction, fasciculations, respiratory embarrassment from chest wall weakness, Grade 3 features not resolving on drug dose reduction.

133

APPENDICES

Appendix 6: Guidelines for adverse drug reaction (ADR) reporting


National Pharmacovigilance Programme
The Medicines Control Council (MCC) has a responsibility to ensure the safety, efficacy and quality of all medicines used by the South African public. The National Pharmacovigilance Programme is coordinated by the MCC and has two dedicated Units responsible for the monitoring of the safety of medicines. The National Adverse Drug Event Monitoring Centre (NADEMC) in Cape Town monitors the safety of all registered medicines in South Africa. In addition, a focused surveillance unit at MEDUNSA is responsible for monitoring the safety of antiretroviral (ARV) medicines and complementary medicines. The unit at MEDUNSA is also responsible for monitoring the safety of unregistered medicines used during clinical trials.

What is pharmacovigilance?
Pharmacovigilance is defined as the science and activities concerned with the detection, assessment, understanding and prevention of adverse reactions to medicines (i.e. adverse drug reactions or ADRs). The goal of this activity is to improve the safe and rational use of medicines, thereby improving patient care and public health.

What is an ADR?
The Medicines Control Council (MCC) defines an adverse drug reaction (ADR) or adverse reaction as a response to a medicine which is noxious and unintended, including lack of efficacy. It can occur at any dosage and can also result from overdose, misuse or abuse of a medicine.

Who should report ADRs?


All health-care workers, including doctors, dentists, pharmacists, nurses and other health professionals are encouraged to report all suspected adverse reactions to medicines (including vaccines, X-ray contrast media, traditional and herbal remedies). This is especially important when the reaction is not in the package insert, is potentially serious or clinically significant.

134

What happens to a report?


All ADR reports are entered into a national ADR database. Each report is evaluated to assess the causal relationship between the event and the medicine. A well-completed adverse drug reaction/product quality form submitted could result in any of the following: I Additional investigations into the use of the medicine in South Africa I Educational initiatives to improve the safe use of the medicine I Appropriate package insert changes to include the potential for the reaction I Changes in the scheduling or manufacture of the medicine to make it safer The purpose of ADR reporting is to reduce the risks associated with the use of medicines and to ultimately improve patient care.

Will reporting have any negative consequences on the health worker or the patient?
An adverse drug reaction report does not constitute an admission of liability or that the health professional contributed to the event in any way. The outcome of a report, together with any important or relevant information relating to the reaction, will be sent back to the reporter as appropriate. The details of a report are stored in a confidential database. The names of the reporter or any other health professionals named on a report and the patient will be removed before any details about a specific adverse drug reaction are used or communicated to others. The information is only meant to improve the understanding of the medicines used in the country.

Is the event possibly an ADR?


The following factors should be considered when an adverse drug reaction is suspected: 1. What exactly is the nature of the reaction? (Describe the reaction as clearly as you can, and where possible provide an accurate diagnosis.)

135

Appendix 4: ARVs for children side effects and adverse events


Side effects and adverse events of ARVs in children
Class NRTI Drug Zidovidine (Retrovir ) Didanosine ddI (Videx ) Side effects/adverse events Anaemia, granulocytopenia, myopathy, lactic acidosis Common: abdominal pain, nausea and vomiting Uncommon: pancreatitis, peripheral neuropathy, lactic acidosis Stavudine Common: headache, rash, gastrointestinal (Zerit ) Uncommon: pancreatitis and peripheral neuropathy, lactic acidosis Abacavir Hypersensitivity reaction (with or without rash) may be fatal in adults and children (Ziagen ) Lamivudine Common: headache, fatigue and abdominal pain (3TC) Uncommon: pancreatitis and peripheral neuropathy, lactic acidosis Nevirapine Skin rash, sedative effect and diarrhoea (Viramune ) LIVER TOXICITY Efavirenz Skin rash CNS Sleep disturbance, confusion, abnormal (Stocrin ) thinking. Teratogenic in primates Ritonavir Nausea, vomiting, diarrhoea (Norvir ) Hypercholesterolaemia and hypertriglyceridaemia Nelfinavir Diarrhoea (Viracept ) Can exacerbate chronic liver disease Hypercholesterolaemia and hypertriglyceridaemia Nausea, vomiting, diarrhoea Kaletra Hypercholesterolaemia and hypertriglyceridaemia

NNRTI

PI

131

APPENDICES

Appendix 5: Grading of adverse events


Feature Haematology Haemoglobin (g/dL) Age >2 yrs Absolute neutrophil count Platelets (cells/mm) Gastro-intestinal Bilirubin AST ALT GT Pancreatic Amylase Abdominal pain Diarrhoea Grade 1 1010.9 Grade 2 79.9 Grade 3 <7.0 Grade 4 Cardiac failure 2 to anaemia

0.750 1.2

0.4000.749 50 00075 000

0.250.399 25 00049.999

<0.250 <25 000 or bleeding

1.11.9 x N* 1.14.9 x N 1.14.9 x N 1.14.9 x N 1.11.4 x N Mild Soft stools

2.02.9 x N 5.09.9 x N 5.09.9 x N 5.09.9 x N 1.51.9 x N Moderate No Rx needed Liquid stools

3.07.5 x N 10.015.0 x N 10.015.0 x N 10.015.0 x N 2.03.0 x N Moderate Rx needed Liquid stools + mild dehydration, bloody stools Severe Severe, little oral intake >3 episodes/ day or duration >7 days Mild urticaria >40C

>7.5 x N >15.0 x N >15.0 x N >15.0 x N >3.0 x N Hospital and Rx Severe dehydration or hypotensive shock Distention + vomiting Unable to take any food or fluid for >24 hrs Intractable vomiting

Constipation Nausea

Mild Mild

Moderate Moderate

Vomiting

<1 episode/ 13 episodes/ day day or duration >3 days Allergic/dermatalogical Allergy Itch without Itchy rash rash Drug fever 38.540.0C Cutaneous

Diffuse macu- Vesiculation, papular rash dry ulcers desquamation

Severe urticaria Anaphylaxis, angioedema Sustained fever: >40C >5 days Exfoliative dermatitis, StevenJohnson or E. multiforme, moist desquamation

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Feature

Grade 1

Grade 2

Grade 3 Changes not improved with drugs or other therapy: or onset of confusion, memory loss, lethargy, sedation, or somnolence not resolved by rest See below**

Grade 4 Delirium, obtundation, coma or psychosis or Grade 3 toxicity with no response to dose reduction

Nervous system Mental status or Changes with Changes behaviour normal requiring drugs function or other therapy: or mild lethargy, sedation, or somnolence that resolves with rest

Neuropathy/ lower motor neuropathy Other Clinical symptoms not otherwise specified above

None

Mild transient parathesia

See below***

No therapy, monitor condition

May require Requires Requires active medical minimal care or possible intervention, hospitalisation intervention and hospitalisation or hospice care monitoring

* N = normal ** Persistent or progressive parasthesias, burning sensation of feet or mild disethesia, no weakness, mild tendon reflex changes, no sensory loss. *** Onset of significant weakness, decrease or loss of DTR, sensory loss in stocking-glove distribution, multiple cranial nerve involvement; bladder or bowel dysfunction, fasciculations, respiratory embarrassment from chest wall weakness, Grade 3 features not resolving on drug dose reduction.

133

APPENDICES

Appendix 6: Guidelines for adverse drug reaction (ADR) reporting


National Pharmacovigilance Programme
The Medicines Control Council (MCC) has a responsibility to ensure the safety, efficacy and quality of all medicines used by the South African public. The National Pharmacovigilance Programme is coordinated by the MCC and has two dedicated Units responsible for the monitoring of the safety of medicines. The National Adverse Drug Event Monitoring Centre (NADEMC) in Cape Town monitors the safety of all registered medicines in South Africa. In addition, a focused surveillance unit at MEDUNSA is responsible for monitoring the safety of antiretroviral (ARV) medicines and complementary medicines. The unit at MEDUNSA is also responsible for monitoring the safety of unregistered medicines used during clinical trials.

What is pharmacovigilance?
Pharmacovigilance is defined as the science and activities concerned with the detection, assessment, understanding and prevention of adverse reactions to medicines (i.e. adverse drug reactions or ADRs). The goal of this activity is to improve the safe and rational use of medicines, thereby improving patient care and public health.

What is an ADR?
The Medicines Control Council (MCC) defines an adverse drug reaction (ADR) or adverse reaction as a response to a medicine which is noxious and unintended, including lack of efficacy. It can occur at any dosage and can also result from overdose, misuse or abuse of a medicine.

Who should report ADRs?


All health-care workers, including doctors, dentists, pharmacists, nurses and other health professionals are encouraged to report all suspected adverse reactions to medicines (including vaccines, X-ray contrast media, traditional and herbal remedies). This is especially important when the reaction is not in the package insert, is potentially serious or clinically significant.

134

What happens to a report?


All ADR reports are entered into a national ADR database. Each report is evaluated to assess the causal relationship between the event and the medicine. A well-completed adverse drug reaction/product quality form submitted could result in any of the following: I Additional investigations into the use of the medicine in South Africa I Educational initiatives to improve the safe use of the medicine I Appropriate package insert changes to include the potential for the reaction I Changes in the scheduling or manufacture of the medicine to make it safer The purpose of ADR reporting is to reduce the risks associated with the use of medicines and to ultimately improve patient care.

Will reporting have any negative consequences on the health worker or the patient?
An adverse drug reaction report does not constitute an admission of liability or that the health professional contributed to the event in any way. The outcome of a report, together with any important or relevant information relating to the reaction, will be sent back to the reporter as appropriate. The details of a report are stored in a confidential database. The names of the reporter or any other health professionals named on a report and the patient will be removed before any details about a specific adverse drug reaction are used or communicated to others. The information is only meant to improve the understanding of the medicines used in the country.

Is the event possibly an ADR?


The following factors should be considered when an adverse drug reaction is suspected: 1. What exactly is the nature of the reaction? (Describe the reaction as clearly as you can, and where possible provide an accurate diagnosis.)

135

APPENDICES
2. Did the reaction occur within a reasonable time relationship to starting treatment with the suspected medicine? (Some reactions occur immediately after administration of a medicine while others take time to develop.) 3. Is the reaction known to occur with the particular medicine as stated in the package insert or other reference? (If the reaction is not documented in the package insert, it does not mean that the reaction cannot occur with that particular medicine.) 4. Did the patient recover when the suspected medicine was stopped? (Some reactions can cause permanent damage, but most reactions are reversible if the medication is stopped.) 5. Did the patient take the medicine again after the reaction abated (i.e. rechallenge). If so, did the same reaction occur again? (In most situations it is not possible or ethical to rechallenge the patient with the same medicine. If such information is available or if such a rechallenge is necessary, recurrence of the event is a strong indicator that the medicine may be responsible.) 6. Can this reaction be explained by other causes (e.g. underlying disease(s); other medicine(s); toxins or foods)? (It is essential that the patient is thoroughly investigated to decide what the actual cause of any new medical problem is. A medicinerelated cause should be considered, when other causes do not explain the patients condition.)

What types of reactions should be reported?


The following ADRs should be reported: I All ADRs to newly marketed drugs or new drugs added to the EDL I All serious reactions and interactions I ADRs that are not clearly stated in the package insert I All adverse reactions to or poisonings from traditional or herbal remedies Report even if you are not certain that the medicine caused the event.

136

What product quality problems should be reported?


The following product quality problems should be reported: I Suspected contamination I Questionable stability I Defective components I Poor packaging or labelling I Therapeutic failures

How can ADRs be prevented from occurring?


Some ADRs are unavoidable and cannot be prevented. However, most ADRs can be prevented by following the basic principles of rational use of medicines.

How are ADRs reported?


An Adverse Drug Reaction/Product Quality Report Form is enclosed in this book and should be completed in as much detail as possible before returning it by fax or post to any of the addresses provided below. Additional forms can be obtained by contacting the MCC at these addresses. Report forms may also be accessed via the following website: http://www.mccza.com 1. The Registrar of Medicines Medicines Control Council, Department of Health, Private Bag X828, Pretoria, 0001 Tel: (012) 312-0925; Fax: (012) 312-0925 2. The National Adverse Drug Event Monitoring Centre (NADEMC) c/o Division of Pharmacology, University of Cape Town, Observatory, 7925 Tel: (021) 447-1618; Fax: (021) 448-6181 For spontaneous reporting, including HIV and AIDS 3. MEDUNSA Pharmacovigilance Unit Tel. (012) 521-4358; Fax (012) 521-4335 For adults and adolescents 4. University of Free State Pharmacovigilance Unit For pregnant women and children Not yet operational

137

138
Adverse reaction1

Adverse Drug Reaction and Product Quality Problem Report Form

APPENDICES

(Identities of reporter and patient will remain strictly confidential)


NATIONAL ADVERSE DRUG EVENT MONITORING CENTRE Medicines Control Council, The Registrar of Medicines, Department of Health In collaboration with the WHO International Drug Monitoring Programme Tel : (021) 447-1618 Fax: ( 021) 448-6181

Appendix 7: Adverse drug reaction and product quality problem report form

PATIENT INFORMATION

Name (or initials):................................................. Age:................. Weight (kg):.............................. Sex: M F Date of birth:......... / ........./ .......... Height (cm):............................
ADVERSE REACTION/PRODUCT QUALITY PROBLEM

and/or Product Quality Problem2

Date of onset of reaction:......./......../...... Time of onset of reaction:.......h.........min

Description of reaction or problem (Include relevant tests/lab data, as well as dates):


1. ADVERSE REACTION PROBLEM
MEDICINES/VACCINES/DEVICES (include all concomitant medicines)

Trade Name (Asterisk*


suspected product)

Batch No.

Daily Dosage

Route

Date Started

Date Stopped

Reasons for use

ADVERSE REACTION OUTCOME (Check all that apply)

death disability congenital anomaly required intervention to prevent permanent impairment/damage

life-threatening hospitalisation other................... ........................... ........................... ........................... ...........................

Event reappeared on rechallenge: Y N Rechallenge not done Treatment (of reaction): ...................................... ...................................... ......................................

Recovered: Y Sequelae:
Y

N N

Describe sequelae: ............................. ............................. ............................. .............................

COMMENTS: (e.g. relevant history, allergies, previous exposure, baseline test results/lab data)

2. PRODUCT QUALITY PROBLEM Trade Name Batch No Registration No Dosage form & strength Expiry Date Size/Type of container

Product available for evaluation?

Reporting doctor/pharmacist etc: Name: ................................................................... Qualifications:.......................................... Address: ............................................................................................................................................ Signature:..................................... Date:.................................... Tel: (.........)...................................
This report does not constitute an admission that medical personnel or the product caused or contributed to the event.

139

APPENDICES
Advice about voluntary reporting
Report adverse experiences with: I Medications (drugs, vaccines and biologicals) I Medical devices (including in-vitro diagnostics) I Traditional and herbal remedies I For adverse events following immunisation (AEFI), please follow the reporting procedure recommended by the Expanded Programme in Immunisation (EPI) Please report: Adverse drug reactions to recently marketed products I Serious reactions and interactions with all products I Adverse drug reactions which are not clearly reflected in the package insert
I

Report even if: Youre not certain the product caused the event. I You dont have all the details.
I

Report product quality problems such as: I Suspected contamination I Questionable stability I Defective components I Poor packaging or labelling I Therapeutic failures Important numbers: Investigational products and product quality problems: I (012) 326-4344 to fax a report I (012) 312-0000 to report by phone Registered medicines and traditional and herbal remedies: I (021) 448-6181 to fax a report I (021) 447-1618 to report by phone

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Adverse events following immunisation: I (012) 312-0110 to phone for information I (012) 321-9882 to fax a report Confidentiality: Identities of the reporter and patient will remain strictly confidential. Your support of the Medicine Control Councils adverse drug reaction monitoring programme is much appreciated. Information supplied by you will contribute to the improvement of drug safety and therapy in South Africa. PLEASE POST FORMS TO THE ADDRESS PROVIDED BELOW Department of Health Registrar of Medicines Private bag x828 Pretoria 0001

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ACRONYMS AND ABBREVIATIONS


AFB AIDS ART AZT CB ddI D4T ELISA GIT HAART HIV IMCI IRIS LIP MAC NDoH NVP OI ORS PCP PCR PHC SSS STI TB 3TC Acid Fast Bacilli Acquired Immunodeficiency Syndrome Antiretroviral Therapy Zidovudine Chart Booklet (Integrated Management of Childhood Illness) Didanosine Stavudine Enzyme-linked Immunosorbent Assay Gastrointestinal Tract Highly Active Antiretrovairal Therapy Human Immunodeficiency Virus Integrated Management of Childhood Illnesses Immune Reconstitution Inflammatory Syndrome Lymphocytic Interstitial Pneumonitis Mycobactrium avium Intracellulare National Department of Health Nevirapine Opportunistic Infection Oral Rehydration Salts Pneumocystis jiroveci Pneumonia Pneumocystis carinii Pneumonia Polymerase Chain Reaction Primary Health Care Sugar Salt Solution Sexually Transmitted Infection Tuberculosis Lamivudine

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000159